Редактирование: AHR

Aryl hydrocarbon receptor precursor (Ah receptor) (AhR) (Class E basic helix-loop-helix protein 76) (bHLHe76) [BHLHE76]

==Publications==

{{medline-entry
|title=Indoles from the commensal microbiota act via the [[AHR]] and IL-10 to tune the cellular composition of the colonic epithelium during aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32817517
|abstract=The intestinal epithelium is a highly dynamic structure that rejuvenates in response to acute stressors and can undergo alterations in cellular composition as animals age. The microbiota, acting via secreted factors related to indole, appear to regulate the sensitivity of the epithelium to stressors and promote epithelial repair via IL-22 and type I IFN signaling. As animals age, the cellular composition of the intestinal epithelium changes, resulting in a decreased proportion of goblet cells in the colon. We show that colonization of young or geriatric mice with bacteria that secrete indoles and various derivatives or administration of the indole derivative indole-3 aldehyde increases proliferation of epithelial cells and promotes goblet cell differentiation, reversing an effect of aging. To induce goblet cell differentiation, indole acts via the xenobiotic aryl hydrocarbon receptor to increase expression of the cytokine IL-10. However, the effects of indoles on goblet cells do not depend on type I IFN or on IL-22 signaling, pathways responsible for protection against acute stressors. Thus, indoles derived from the commensal microbiota regulate intestinal homeostasis, especially during aging, via mechanisms distinct from those used during responses to acute stressors. Indoles may have utility as an intervention to limit the decline of barrier integrity and the resulting systemic inflammation that occurs with aging.
|mesh-terms=* Aging
* Animals
* Bacteria
* Cell Differentiation
* Epithelial Cells
* Female
* Goblet Cells
* Indoles
* Interleukin-10
* Interleukins
* Male
* Mice
* Mice, Inbred BALB C
* Mice, Inbred C57BL
* Mice, Knockout
* Microbiota
* Mucus
* Receptors, Aryl Hydrocarbon
* Signal Transduction
|keywords=* aging
* goblet cell
* intestinal homeostasis
* mucus
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474656
}}
{{medline-entry
|title=Role of the Aryl Hydrocarbon Receptor in Environmentally Induced Skin Aging and Skin Carcinogenesis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31795255
|abstract=The skin is constantly exposed to a variety of environmental threats, including solar electromagnetic radiation, microbes, airborne particulate matter, and chemicals. Acute exposure to these environmental factors results in the activation of different signaling pathways that orchestrate adaptive stress responses to maintain cell and tissue homeostasis. Chronic exposure of skin to these factors, however, may lead to the accumulation of damaged macromolecules and loss of cell and tissue integrity, which, over time, may facilitate aging processes and the development of aging-related malignancies. One transcription factor that is expressed in all cutaneous cells and activated by various environmental stressors, including dioxins, polycyclic aromatic hydrocarbons, and ultraviolet radiation, is the aryl hydrocarbon receptor ([[AHR]]). By regulating keratinocyte proliferation and differentiation, epidermal barrier function, melanogenesis, and immunity, a certain degree of [[AHR]] activity is critical to maintain skin integrity and to adapt to acute stress situations. In contrast, a chronic activation of cutaneous [[AHR]] signaling critically contributes to premature aging and the development of neoplasms by affecting metabolism, extracellular matrix remodeling, inflammation, pigmentation, DNA repair, and apoptosis. This article provides an overview of the detrimental effects associated with sustained [[AHR]] activity in chronically stressed skin and pinpoints [[AHR]] as a promising target for chemoprevention.
|mesh-terms=* Animals
* Environmental Exposure
* Extracellular Matrix
* Humans
* Receptors, Aryl Hydrocarbon
* Skin Aging
* Skin Neoplasms
|keywords=* DNA damage
* UV radiation
* extracellular matrix
* extrinsic skin aging
* melanoma
* particulate matter
* pigmentation
* polycyclic aromatic hydrocarbons
* squamous cell carcinoma
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928879
}}
{{medline-entry
|title=Loss of Neurogenesis in Aging Hydra.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30912256
|abstract=In Hydra the nervous system is composed of neurons and mechanosensory cells that differentiate from interstitial stem cells (ISCs), which also provide gland cells and germ cells. The adult nervous system is actively maintained through continuous de novo neurogenesis that occurs at two distinct paces, slow in intact animals and fast in regenerating ones. Surprisingly Hydra vulgaris survive the elimination of cycling interstitial cells and the subsequent loss of neurogenesis if force-fed. By contrast, H. oligactis animals exposed to cold temperature undergo gametogenesis and a concomitant progressive loss of neurogenesis. In the cold-sensitive strain Ho_CS, this loss irreversibly leads to aging and animal death. Within four weeks, Ho_CS animals lose their contractility, feeding response, and reaction to light. Meanwhile, two positive regulators of neurogenesis, the homeoprotein prdl-a and the neuropeptide Hym-355, are no longer expressed, while the "old" RFamide-expressing neurons persist. A comparative transcriptomic analysis performed in cold-sensitive and cold-resistant strains confirms the downregulation of classical neuronal markers during aging but also shows the upregulation of putative regulators of neurotransmission and neurogenesis such as [[AHR]], FGFR, FoxJ3, Fral2, Jagged, Meis1, Notch, Otx1, and [[TCF15]]. The switch of Fral2 expression from neurons to germ cells suggests that in aging animals, the neurogenic program active in ISCs is re-routed to germ cells, preventing de novo neurogenesis and impacting animal survival.
|mesh-terms=* Aging
* Animals
* Cold Temperature
* Eating
* Gene Expression
* Hydra
* Movement
* Nerve Degeneration
* Neurogenesis
* Neurons
* Stem Cells
|keywords=* Hydra nervous system
* adult de novo neurogenesis
* aging
* evolution of neurogenesis
* gametogenesis
* homeoprotein prdl-a
* interstitial stem cells
* neuropeptide Hym-355
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586502
}}
{{medline-entry
|title=Environmental cues received during development shape dendritic cell responses later in life.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30412605
|abstract=Environmental signals mediated via the aryl hydrocarbon receptor ([[AHR]]) shape the developing immune system and influence immune function. Developmental exposure to [[AHR]] binding chemicals causes persistent changes in CD4  and CD8  T cell responses later in life, including dampened clonal expansion and differentiation during influenza A virus (IAV) infection. Naïve T cells require activation by dendritic cells (DCs), and [[AHR]] ligands modulate the function of DCs from adult organisms. Yet, the consequences of developmental [[AHR]] activation by exogenous ligands on DCs later in life has not been examined. We report here that early life activation of [[AHR]] durably reduces the ability of DC to activate naïve IAV-specific CD8  T cells; however, activation of naïve CD4  T cells was not impaired. Also, DCs from developmentally exposed offspring migrated more poorly than DCs from control dams in both in vivo and ex vivo assessments of DC migration. Conditional knockout mice, which lack Ahr in CD11c lineage cells, suggest that dampened DC emigration is intrinsic to DCs. Yet, levels of chemokine receptor 7 (CCR7), a key regulator of DC trafficking, were generally unaffected. Gene expression analyses reveal changes in Lrp1, Itgam, and Fcgr1 expression, and point to alterations in genes that regulate DC migration and antigen processing and presentation as being among pathways disrupted by inappropriate [[AHR]] signaling during development. These studies establish that [[AHR]] activation during development causes long-lasting changes to DCs, and provide new information regarding how early life environmental cues shape immune function later in life.
|mesh-terms=* Aging
* Animals
* Bone Marrow Cells
* CD11c Antigen
* CD4-Positive T-Lymphocytes
* CD8-Positive T-Lymphocytes
* Cell Differentiation
* Cell Movement
* Dendritic Cells
* Female
* Gene Expression Regulation, Developmental
* Immune System
* Influenza A Virus, H3N2 Subtype
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Polychlorinated Dibenzodioxins
* Receptors, Aryl Hydrocarbon
* Receptors, CCR7

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226176
}}
{{medline-entry
|title=Nursing Home Use After Implantable Cardioverter-Defibrillator Implantation in Older Adults: Results from the National Cardiovascular Data Registry.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28198561
|abstract=To evaluate the incidence and characteristics of nursing home (NH) use after implantable cardioverter-defibrillator (ICD) implantation. Cohort study. Medicare beneficiaries in the National Cardiovascular Data Registry-ICD Registry. Individuals aged 65 and older receiving ICDs between January 1, 2006, and March 31, 2010 (N = 192,483). Proportion of ICD recipients discharged to NHs directly after device placement, cumulative incidence of long-term NH admission, and factors associated with immediate discharge to a NH and time to long-term NH admission. Over 4 years, 40.6% of the cohort died, and 35,939 (18.7%) experienced at least one NH admission, including 4.0% directly discharged to a NH after ICD implantation and 2.8% admitted to long-term NH care during follow-up. The cumulative incidence of long-term NH admission, accounting for the competing risk of death, was 1.7% at 1 year, 3.8% at 3 years, and 4.6% at 4 years; 20.1% of individuals admitted to a NH died there. Factors most strongly associated with direct NH discharge and time to long-term NH care were older age (adjusted odds ratio (AOR) = 2.09, 95% confidence interval (CI) = 2.01-2.17 per 10-year increment; adjusted hazard ratio ([[AHR]]) = 1.88, 95% CI = 1.80-1.97, respectively), dementia (AOR = 2.60, 95% CI = 2.25-3.01; [[AHR]] = 2.50, 95% CI = 2.14-2.93, respectively), and Medicare Part A claim for NH stay in prior 6 months (AOR = 3.96, 95% CI = 3.70-4.25; [[AHR]] = 2.88, 95% CI = 2.65-3.14, respectively). Nearly one in five individuals are admitted to NHs over a median of 1.6 years of follow-up after ICD implantation. Understanding these outcomes may help inform the clinical care of these individuals.
|mesh-terms=* Age Factors
* Aged
* Cohort Studies
* Defibrillators, Implantable
* Dementia
* Diabetes Mellitus
* Female
* Humans
* Male
* Medicare Part A
* Nursing Homes
* Patient Admission
* Registries
* Sex Factors
* United States
|keywords=* aging
* implantable cardioverter-defibrillators
* outcomes
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325141
}}
{{medline-entry
|title=Genetic variants associated with skin aging in the Chinese Han population.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28057405
|abstract=The progression and manifestation of human skin aging has a strong genetic basis; however, most of the supporting evidence has been gathered in Caucasian populations. The genetic contribution to the variation in skin aging in non-Caucasian populations is poorly understood. To investigate the genetic risk factors of relevance for skin aging in East Asians, we conducted the first candidate gene study for signs of skin aging in Han Chinese. We collected skin aging and genotype data in 502 female Han Chinese from the Taizhou cohort. We evaluated skin aging by the validated skin aging score SCINEXA™. Confounding factors were assessed through a questionnaire. We obtained the genotype data for 21 candidate SNPs and for a further 509 SNPs from 16 related candidate genes. Associations were tested by linear and logistic regression analyses and adjusted for potential confounders. Our candidate study found a significant association between SNP rs2066853 in exon 10 of the aryl hydrocarbon receptor gene [[AHR]] and crow's feet. In addition, we found a significant association between SNP rs10733310 in intron 5 of [[BNC2]] and pigment spots on the arms, and between SNP rs11979919, 3kb downstream of [[COL1A2]], and laxity of eyelids. Our results identified genetic risk factors for signs of skin aging (pigmentation, wrinkles or laxity) in Han Chinese. We also found that the manifestation of skin aging is further modified by anatomical site. Together with previous work, our results also suggest that different genetic variants could be responsible for distinct skin aging signs characteristic of Caucasians compared to East Asians.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Asian Continental Ancestry Group
* Female
* Genetic Association Studies
* Genetic Variation
* Genotype
* Humans
* Middle Aged
* Polymorphism, Single Nucleotide
* Risk Factors
* Skin Aging
* Surveys and Questionnaires
|keywords=* Candidate SNPs
* Candidate genes
* Chinese Han population
* Skin aging
|full-text-url=https://sci-hub.do/10.1016/j.jdermsci.2016.12.017
}}
{{medline-entry
|title=Smoking and Obesity Increase Airway Hyperesponsiveness Risk in the Elderly.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27071476
|abstract=of our study was assessing whether smoking and obesity might affect airways hyperresponsiveness ([[AHR]]) differently in younger and older subjects and whether this influence might be due to their different impacts on baseline lung function values at different ages. 3,903 consecutive adult subjects with normal lung function (1,920 males; mean age 35.1±16.2; median FEV1:97.3% of predicted [interquartile range (IQR):89.7-105.2] and FEV1/FVC: 84.6% of predicted [IQR:79.8-89.2]), having performed a methacholine test, were considered. They were subdivided into three groups according to age (18-39, 40-64 and ≥ 65 years) and into different sub-groups according to body mass index (BMI) and smoking habits, considering two [[AHR]] level cut-offs (PD20≤ 1600 μg and PD20≤ 800 μg). PD20 was significantly lower (p<0.004) in obese subjects aged 18-39 years, in comparison to older patients. Smoking was an [[AHR]] risk factor for subjects aged 40-64 and especially for those aged >65 (OR: 12.786 [IQR: 1.450-112.753]; p<0.0001). Obesity caused an [[AHR]] risk only in older subjects (>65 years) (OR: 3.120 [IQR: 1.144-8.509]; p<0.0001). FEV1/FVC and FEF25-75% decreased progressively (p<0.001) with age in subjects with different weights/smoking habits. No reductions with age were observed in FEV1% and FVC% except for a significant FVC% decrease in older smokers compared to older non-smokers. Smoking determined a progressively increasing [[AHR]] risk reaching its peak in the elderly. In younger obese individuals, [[AHR]] was higher than in obese elderly, whereas obesity was a higher [[AHR]] risk factor only in subjects aged >65 years. A small airway age-related reduction may cause the increased smoking/obesity induced [[AHR]] risk in older people.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aging
* Bronchial Provocation Tests
* Female
* Forced Expiratory Volume
* Humans
* Male
* Methacholine Chloride
* Middle Aged
* Obesity
* Respiratory Hypersensitivity
* Retrospective Studies
* Risk Factors
* Smoking
* Vital Capacity
* Young Adult

|full-text-url=https://sci-hub.do/10.2174/1874609809666160413113604
}}
{{medline-entry
|title=Impaired glucose and lipid metabolism in ageing aryl hydrocarbon receptor deficient mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26664351
|abstract=Disturbed homeostasis of glucose and lipid metabolism are dominant features of the so-called metabolic syndrome (MetS) and can increase the risk for the development of type 2 diabetes (T2D), a severe metabolic disease. T2D prevalence increases with age. The aryl hydrocarbon receptor ([[AHR]]) is a sensor of small molecules including dietary components. [[AHR]] has been identified as potential regulator of glucose homeostasis and lipid metabolism. Epidemiologically, exposure to xenobiotic [[AHR]] ligands such as polycyclic aromatic hydrocarbons is linked to T2D. We assess here the potential role of the [[AHR]] in disturbances of glucose and lipid metabolism in young (age 2-5 months) and old (age > 1,5 years) [[AHR]]-deficient ([[AHR]] KO) mice. Fasted young wildtype (WT) and [[AHR]]-KO mice displayed similar blood glucose kinetics after challenge with intra-peritoneal glucose injection. However, old [[AHR]]-KO mice showed lower tolerance than WT to i.p. administered glucose, i.e. glucose levels rose higher and returned more slowly to normal levels. Old mice had overall higher insulin levels than young mice, and old [[AHR]]-KO had a somewhat disturbed insulin kinetic in the serum after glucose challenge. Surprisingly, young [[AHR]]-KO mice had significantly lower triglycerides, cholesterol, high density lipoprotein values than WT, i.e., a dyslipidemic profile. With ageing, [[AHR]]-KO and WT mice did not differ in these lipid levels, except for slightly reduced levels of triglycerides and cholesterol. In conclusion, our findings in [[AHR]] KO mice suggest that [[AHR]] expression is relevant for the maintenance of glucose and lipid homeostasis in old mice. 

|keywords=* AHR
* diet
* dyslipidemia
* metabolic syndrome
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673916
}}
{{medline-entry
|title=Enhanced allergic airway disease in old mice is associated with a Th17 response.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25109604
|abstract=The prevalence of asthma in the elderly is increasing and associated with higher mortality than in children or young adults. However, the effects of age on the development and character of allergic asthma have been understudied. It has been suggested that mixed Th2/Th17 responses cause more severe forms of asthma, but the role of Th17 response in allergic airway disease and aging is not well understood. To investigate age-dependent characteristics and Th17 immune response in allergic airway disease in a murine house dust mite (HDM)-allergen model. Twelve-week-old and 15-month-old male BALB/c mice were sensitized and challenged with HDM. Bronchoalveolar lavage fluid (BALF), airway inflammation and hyperresponsiveness ([[AHR]]), serum immunoglobulin and splenic T cells were assessed. Age-related T cell activation was analyzed in a co-culture with bone marrow-derived dendritic cells (BMDC) and splenic CD4( ) T cells from young and old mice. Features of allergic airway disease such as mucous cell hyperplasia, infiltration of airway eosinophils and lymphocytes, Th2 cytokine expression and serum IgG1 levels were greater in old compared to young mice. In contrast to the more marked inflammatory/immune responses to HDM in old mice, [[AHR]] was greater in young HDM-treated mice. Only the old mice developed airway neutrophil infiltration and a Th17 immune response upon HDM exposure, with increases in BALF cytokines IL-17A and KC, and Th17 cytokine producing T cells in the spleen. Stimulation of CD4( ) T cells and BMDC co-cultures with HDM, resulted in an enhanced Th17 cytokine response in cells isolated from old mice. Our findings in mice suggest that the severity and character of allergic airway disease are age dependent, with a bias towards a Th17 immune response with aging. Elderly, asthmatics may be prone to develop severe allergic airway inflammation with a mixed Th2/Th17 immune response.
|mesh-terms=* Age Factors
* Animals
* Asthma
* CD4-Positive T-Lymphocytes
* Cytokines
* Dendritic Cells
* Immunoglobulin G
* Male
* Mice
* Mice, Inbred BALB C
* Pyroglyphidae
* Th17 Cells
* Th2 Cells
|keywords=* Th17
* aging
* allergic asthma
* house dust mite
* mice
|full-text-url=https://sci-hub.do/10.1111/cea.12388
}}
{{medline-entry
|title=Influenza A infection enhances antigen-induced airway inflammation and hyperresponsiveness in young but not aged mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25039815
|abstract=Although morbidity and mortality rates from asthma are highest in patients > 65 years of age, the effect of older age on airway inflammation in asthma is not well established. To investigate age-related differences in the promotion of allergic inflammation after influenza A viral respiratory infection on antigen-specific IgE production, antigen-induced airway inflammation and airway hyperresponsiveness in mice. To accomplish this objective, the following model system was used. Young (6 week) and aged (18 months) BALB/c mice were first infected with a non-lethal dose of influenza virus A (H/HKx31). Mice were then ovalbumin (OVA)-sensitized during the acute infection (3-days post inoculation) and then chronically underwent challenge to the airways with OVA. Forty-eight hours after the final OVA challenge, airway hyperresponsiveness ([[AHR]]), bronchoalveolar fluid (BALF) cellular and cytokine profile, antigen-specific IgE and IgG1, and lung tissue inflammation were measured. Age-specific differences were noted on the effect of a viral infection, allergic sensitization, airway inflammation and airway hyperresponsiveness. Serum OVA-specific IgE was significantly increased in only the aged mice infected with influenza virus. Despite greater morbidity (e.g. weight loss and sickness scores) during the acute infection in the 18-month old mice that were OVA-sensitized, there was little effect on the [[AHR]] and BALF cellular differential. In contrast, BALF neutrophils and [[AHR]] increased, but eosinophils decreased in 6-week mice that were OVA-sensitized during an acute influenza infection. With increased age in a mouse model, viral infection prior to antigen sensitization affects the airway and systemic allergic response differently. These differences may reflect distinct phenotypic features of allergic inflammation in older patients with asthma.
|mesh-terms=* Age Factors
* Animals
* Antigens
* Asthma
* Bronchoalveolar Lavage Fluid
* Cytokines
* Disease Models, Animal
* Female
* Immunoglobulin E
* Influenza A virus
* Leukocyte Count
* Lung
* Mice
* Orthomyxoviridae Infections
* Ovalbumin
* Respiratory Hypersensitivity
|keywords=* aging
* asthma
* influenza
* murine model
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643670
}}
{{medline-entry
|title=A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24655420
|abstract=Although dietary restriction (DR) is known to extend lifespan across species, from yeast to mammals, the signalling events downstream of food/nutrient perception are not well understood. In Caenorhabditis elegans, DR is typically attained either by using the eat-2 mutants that have reduced pharyngeal pumping leading to lower food intake or by feeding diluted bacterial food to the worms. In this study, we show that knocking down a mammalian MEKK3-like kinase gene, mekk-3 in C. elegans, initiates a process similar to DR without compromising food intake. This DR-like state results in upregulation of beta-oxidation genes through the nuclear hormone receptor NHR-49, a HNF-4 homolog, resulting in depletion of stored fat. This metabolic shift leads to low levels of reactive oxygen species (ROS), potent oxidizing agents that damage macromolecules. Increased beta-oxidation, in turn, induces the phase I and II xenobiotic detoxification genes, through PHA-4/FOXA, NHR-8 and aryl hydrocarbon receptor [[AHR]]-1, possibly to purge lipophilic endotoxins generated during fatty acid catabolism. The coupling of a metabolic shift with endotoxin detoxification results in extreme longevity following mekk-3 knock-down. Thus, MEKK-3 may function as an important nutrient sensor and signalling component within the organism that controls metabolism. Knocking down mekk-3 may signal an imminent nutrient crisis that results in initiation of a DR-like state, even when food is plentiful. 
|mesh-terms=* Animals
* Biotransformation
* Caenorhabditis elegans
* Caenorhabditis elegans Proteins
* Caloric Restriction
* Conserved Sequence
* Electron Transport Complex II
* Fatty Acids
* Gene Knockdown Techniques
* Inactivation, Metabolic
* Insulin
* Longevity
* Muscles
* Oligonucleotide Array Sequence Analysis
* Oxidation-Reduction
* Protein-Serine-Threonine Kinases
* Reactive Oxygen Species
* Signal Transduction
* Subcutaneous Tissue
* Transcription Factors
* Transforming Growth Factor beta
* Up-Regulation
* Xenobiotics
|keywords=* Caenorhabditis elegans
* beta-oxidation
* dietary restriction
* fat storage
* lifespan
* xenobiotic detoxification
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326946
}}
{{medline-entry
|title=Early postnatal, but not late, exposure to chemical ambient pollutant 1,2-naphthoquinone increases susceptibility to pulmonary allergic inflammation at adulthood.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24554396
|abstract=High diesel exhaust particle levels are associated with increased health effects; however, knowledge on the impact of its chemical contaminant 1,2-naphthoquinone (1,2-NQ) is limited. We investigated whether postnatal and adult exposures to 1,2-NQ influence allergic reaction and the roles of innate and adaptive immunity. Male neonate (6 days) and adult (56 days) C57Bl/6 mice were exposed to 1,2-NQ (100 nM; 15 min) for 3 days, and on day 59, they were sensitized and later challenged with ovalbumin (OVA). Airway hyper-responsiveness ([[AHR]]) and production of cytokines, immunoglobulin E (IgE) and leukotriene B4 (LTB4) were measured in the airways. Postnatal exposure to 1,2-NQ activated dendritic cells in splenocytes by increasing expressing cell surface molecules (e.g., CD11c). Co-exposure to OVA effectively polarized T helper (Th) type 2 (Th2) by secreting Th2-mediated cytokines. Re-stimulation with unspecific stimuli (PMA and ionomycin) generated a mixed Th1 (CD4( )/IFN-γ( )) and Th17 (CD4( )/IL-17( )) phenotype in comparison with the vehicle-matched group. Postnatal exposure to 1,2-NQ did not induce eosinophilia in the airways at adulthood, although it evoked neutrophilia and exacerbated OVA-induced eosinophilia, Th2 cytokines, IgE and LTB4 production without affecting [[AHR]] and mast cell degranulation. At adulthood, 1,2-NQ exposure evoked neutrophilia and increased Th1/Th2 cytokine levels, but failed to affect OVA-induced eosinophilia. In conclusion, postnatal exposure to 1,2-NQ increases the susceptibility to antigen-induced asthma. The mechanism appears to be dependent on increased expression of co-stimulatory molecules, which leads to cell presentation amplification, Th2 polarization and enhanced LTB4, humoral response and Th1/Th2 cytokines. These findings may be useful for future investigations on treatments focused on pulmonary illnesses observed in children living in heavy polluted areas.
|mesh-terms=* Adaptive Immunity
* Aging
* Air Pollutants
* Animals
* Animals, Newborn
* Cytokines
* Disease Susceptibility
* Immunity, Innate
* Immunoglobulin E
* Inhalation Exposure
* Leukotriene B4
* Male
* Naphthoquinones
* Ovalbumin
* Pneumonia
* Respiratory Hypersensitivity
* Vehicle Emissions

|full-text-url=https://sci-hub.do/10.1007/s00204-014-1212-z
}}
{{medline-entry
|title=Airway hyperresponsiveness is associated with airway remodeling but not inflammation in aging Cav1-/- mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24138138
|abstract=Airway inflammation and airway remodeling are the key contributors to airway hyperresponsiveness ([[AHR]]), a characteristic feature of asthma. Both processes are regulated by Transforming Growth Factor (TGF)-β. Caveolin 1 (Cav1) is a membrane bound protein that binds to a variety of receptor and signaling proteins, including the TGF-β receptors. We hypothesized that caveolin-1 deficiency promotes structural alterations of the airways that develop with age will predispose to an increased response to allergen challenge. [[AHR]] was measured in Cav1-deficient and wild-type (WT) mice 1 to 12 months of age to examine the role of Cav1 in [[AHR]] and the relative contribution of inflammation and airway remodeling. [[AHR]] was then measured in Cav1-/- and WT mice after an ovalbumin-allergen challenge performed at either 2 months of age, when remodeling in Cav1-/- and WT mice was equivalent, and at 6 months of age, when the Cav1-/- mice had established airway remodeling. Cav1-/- mice developed increased thickness of the subepithelial layer and a correspondingly increased [[AHR]] as they aged. In addition, allergen-challenged Cav1-/- mice had an increase in [[AHR]] greater than WT mice that was largely independent of inflammation. Cav1-/- mice challenged at 6 months of age have decreased [[AHR]] compared to those challenged at 2 months with correspondingly decreased BAL IL-4 and IL-5 levels, inflammatory cell counts and percentage of eosinophils. In addition, in response to OVA challenge, the number of goblet cells and α-SMA positive cells in the airways were reduced with age in response to OVA challenge in contrast to an increased collagen deposition further enhanced in absence of Cav1. A lack of Cav1 contributed to the thickness of the subepithelial layer in mice as they aged resulting in an increase in [[AHR]] independent of inflammation, demonstrating the important contribution of airway structural changes to [[AHR]]. In addition, age in the Cav1-/- mice is a contributing factor to airway remodeling in the response to allergen challenge.
|mesh-terms=* Actins
* Aging
* Airway Remodeling
* Animals
* Asthma
* Bronchial Hyperreactivity
* Caveolin 1
* Collagen
* Disease Models, Animal
* Female
* Interleukin-4
* Interleukin-5
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Ovalbumin
* Pneumonia
* Transforming Growth Factor beta

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015038
}}
{{medline-entry
|title=Ventilation heterogeneity is associated with airway responsiveness in asthma but not COPD.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23876741
|abstract=Airway hyperresponsiveness ([[AHR]]) occurs in both asthma and COPD. In older people with asthma, [[AHR]] is associated with increased acinar ventilation heterogeneity, but it is unknown if this association exists in COPD. Thirty one COPD and 19 age-matched asthmatic subjects had measures of spirometry, lung volumes, exhaled nitric oxide, ventilation heterogeneity, and methacholine challenge. Indices of acinar (Sacin) and conducting (Scond) airway ventilation heterogeneity were calculated from the multiple breath nitrogen washout. Predictors of [[AHR]] were then determined. In COPD, [[AHR]] was predicted by lower Sacin and lower FVC (model r(2)=0.35, p=0.001). In asthma, [[AHR]] was predicted by higher Sacin and higher residual volume (model r(2)=0.62, p<0.001). These findings suggest that airway responsiveness in COPD and asthma is determined by underlying disease-specific processes, rather than a common pattern of physiological abnormality. 
|mesh-terms=* Aged
* Aged, 80 and over
* Asthma
* Breath Tests
* Bronchial Hyperreactivity
* Bronchial Provocation Tests
* Cross-Sectional Studies
* Female
* Humans
* Lung Volume Measurements
* Male
* Middle Aged
* Plethysmography
* Pulmonary Disease, Chronic Obstructive
* Pulmonary Ventilation
* Spirometry
|keywords=* Aging
* Airway hyperresponsiveness
* Chronic obstructive pulmonary disease
* Physiology
* Pulmonary mechanics
|full-text-url=https://sci-hub.do/10.1016/j.resp.2013.07.009
}}
{{medline-entry
|title=Relationship between airway pathophysiology and airway inflammation in older asthmatics.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23734667
|abstract=Asthma-related morbidity is greater in older compared with younger asthmatics. Airway closure is also greater in older asthmatics, an observation that may be explained by differences in airway inflammation. We hypothesized that in older adult patients with asthma, neutrophil airway inflammation increases airway closure during bronchoconstriction, while eosinophil airway inflammation increases airway hyperresponsiveness ([[AHR]]). Asthmatic subjects (n = 26), aged ≥55 years (68% female), were studied, and [[AHR]] to 4.5% saline challenge was measured by the response-dose ratio (�ll in forced expiratory volume in 1 s (FEV1 )/mg saline). Airway closure was assessed during bronchoconstriction percent change in forced vital capacity (FVC)/percent change in FEV1 (i.e. Closing Index). Airway inflammation was assessed by induced sputum and exhaled nitric oxide (eNO). Mean patient age was 67 years (confidence interval: 63-71) with a mean FEV1 of 78 % predicted (confidence interval: 70-85%). [[AHR]] correlated with sputum eosinophils (r = 0.68, P = 0.005) and eNO (r = 0.71, P < 0.001), but not with neutrophils or neutrophil mediators. The Closing Index correlated with total sputum neutrophils (r = 0.66, P = 0.005), neutrophil elastase, matrix metalloproteinase-9 and interleukin-8 (all P < 0.05). Further, FEV1 /FVC and residual volume/total lung capacity at rest correlated with neutrophil elastase (r = -0.46 and 0.66 respectively, P < 0.05) but not with eosinophils or eNO. In older patients with asthma, airway inflammatory cells are linked to abnormal airway physiology. Eosinophilic airway inflammation is associated with [[AHR]] while neutrophilic inflammation may be an important determinant of airflow limitation at rest and airway closure during bronchoconstriction. The clinical implications of these findings remain to be determined.
|mesh-terms=* Age Factors
* Aged
* Aging
* Asthma
* Bronchoconstriction
* Eosinophils
* Female
* Forced Expiratory Volume
* Humans
* Leukocyte Elastase
* Male
* Matrix Metalloproteinase 9
* Middle Aged
* Neutrophils
* Nitric Oxide
* Pneumonia
* Respiratory Function Tests
* Respiratory System
|keywords=* airway closure
* airway hyper responsiveness
* airway inflammation
* asthma
* elderly
|full-text-url=https://sci-hub.do/10.1111/resp.12142
}}