CXCL8
Interleukin-8 precursor (IL-8) (C-X-C motif chemokine 8) (Chemokine (C-X-C motif) ligand 8) (Emoctakin) (Granulocyte chemotactic protein 1) (GCP-1) (Monocyte-derived neutrophil chemotactic factor) (MDNCF) (Monocyte-derived neutrophil-activating peptide) (MONAP) (Neutrophil-activating protein 1) (NAP-1) (Protein 3-10C) (T-cell chemotactic factor) [Contains: MDNCF-a (GCP/IL-8 protein IV) (IL8/NAP1 form I); Interleukin-8 ((Ala-IL-8)77) (GCP/IL-8 protein II) (IL-8(1-77)) (IL8/NAP1 form II) (MDNCF-b); IL-8(5-77); IL-8(6-77) ((Ser-IL-8)72) (GCP/IL-8 protein I) (IL8/NAP1 form III) (Lymphocyte-derived neutrophil-activating factor) (LYNAP) (MDNCF-c) (Neutrophil-activating factor) (NAF); IL-8(7-77) (GCP/IL-8 protein V) (IL8/NAP1 form IV); IL-8(8-77) (GCP/IL-8 protein VI) (IL8/NAP1 form V); IL-8(9-77) (GCP/IL-8 protein III) (IL8/NAP1 form VI)] [IL8]
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Alzheimer's Disease (AD) is associated with neuropathological changes, including aggregation of tau neurofibrillary tangles (NFTs) and amyloid-beta plaques. Mounting evidence indicates that vascular dysfunction also plays a key role in the pathogenesis and progression of AD, in part through endothelial dysfunction. Based on findings in animal models that tau pathology induces vascular abnormalities and cellular senescence, we hypothesized that tau pathology in the human AD brain leads to vascular senescence. To explore this hypothesis, we isolated intact microvessels from the dorsolateral prefrontal cortex (PFC, BA9) from 16 subjects with advanced Braak stages (Braak V/VI, B3) and 12 control subjects (Braak 0/I/II, B1), and quantified expression of 42 genes associated with senescence, cell adhesion, and various endothelial cell functions. Genes associated with endothelial senescence and leukocyte adhesion, including SERPINE1 (PAI-1), CXCL8 (IL8), CXCL1, CXCL2, ICAM-2, and TIE1, were significantly upregulated in B3 microvessels after adjusting for sex and cerebrovascular pathology. In particular, the senescence-associated secretory phenotype genes SERPINE1 and CXCL8 were upregulated by more than 2-fold in B3 microvessels after adjusting for sex, cerebrovascular pathology, and age at death. Protein quantification data from longitudinal plasma samples for a subset of 13 ([i]n[/i] = 9 B3, [i]n[/i] = 4 B1) subjects showed no significant differences in plasma senescence or adhesion-associated protein levels, suggesting that these changes were not associated with systemic vascular alterations. Future investigations of senescence biomarkers in both the peripheral and cortical vasculature could further elucidate links between tau pathology and vascular changes in human AD.
Keywords
- Alzheimer's disease
- endothelial senescence
- gene expression
- neurofibrillary tangles
- plasma biomarkers
- tau pathology
- vascular dysfunction
In the present study, we aimed to investigate the impact of permanent cystathionine-β-Synthase (CBS) gene knockdown in human telomerase reverse transcriptase (hTERT) immortalized human adipose-derived mesenchymal stem cells (ASC52telo) and in their capacity to differentiate into adipocytes. CBS gene KD in ASC52telo cells led to increased cellular inflammation (IL6, CXCL8, TNF) and oxidative stress markers (increased intracellular reactive oxygen species and decreased reduced glutathione levels) in parallel to decreased H S production and rejuvenation (LC3 and SIRT1)-related gene expression. In addition, CBS gene KD in ASC52telo cells resulted in altered mitochondrial respiratory function, characterised by decreased basal respiration (specifically proton leak) and spare respiratory capacity, without significant effects on cell viability and proliferation. In this context, shCBS-ASC52telo cells displayed enhanced adipogenic (FABP4, ADIPOQ, SLC2A4, CEBPA, PPARG)-, lipogenic (FASN, DGAT1)- and adipocyte (LEP, LBP)-related gene expression markers, decreased expression of proinflammatory cytokines, and increased intracellular lipid accumulation during adipocyte differentiation compared to control ASC52telo cells. Otherwise, the increased adipogenic potential of shCBS-ASC52telo cells was detrimental to the ability to differentiate into osteogenic linage. In conclusion, this study demonstrated that permanent CBS gene KD in ASC52telo cells promotes a cellular senescence phenotype with a very increased adipogenic potential, promoting a non-physiological enhanced adipocyte differentiation with excessive lipid storage.
Keywords
- Cellular senescence
- Cystathionine β-synthase
- Human adipose-derived mesenchymal stem cells
- Inflammation
- Oxidative stress and adipogenesis
Chagas disease is endemic in Latin America and still represents an important public health problem in the region. Chronic cardiomyopathy is the most significant chronic form due to its association with morbidity and mortality. The last decade has seen increasing evidence that inflammatory cytokines and chemokines are responsible for the generation of inflammatory infiltrate and tissue damage, with chronic chagasic cardiomyopathy patients presenting a pro-inflammatory immune response. Although studies have evaluated the role of chemokines in experimental T. cruzi infection, few have addressed their systemic profile, especially for human infection and in aging populations. The present work aimed to use the data from a large population based study of older adults, conducted in an endemic area for Chagas disease, to examine the association between serum levels of cytokines and chemokines, T. cruzi infection and electrocardiogram (ECG) abnormality. The present work evaluated serum levels of CCL2, CXCL9, CXCL10, CCL5, CXCL8, IL-1β, IL-6, TNF, IL-12 and IL-10 by Flow Cytometric Bead Array assay (CBA) and the results expressed in pg/ml. The baseline survey started in January 1st 1997, with 1284 participants of an aged population-based cohort. Participants signed an informed consent at baseline and at each subsequent visit and authorized death certificate and medical records verification. Our results demonstrated that Chagas disease patients had higher serum levels of CXCL9, CXCL10 and IL-1β and lower serum levels of CCL5 than non-infected subjects. Moreover, our data demonstrated that CXCL9 and CXCL10 increased in an age-dependent profile in Chagas disease patients. Together, this study provided evidences that serum biomarkers increase along the age continuum and may have potential implications for establishing clinical management protocols and therapeutic intervention in Chagas disease patients.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Biomarkers
- Brazil
- Chagas Disease
- Chemokine CXCL10
- Chemokine CXCL9
- Cohort Studies
- Electrocardiography
- Female
- Humans
- Male
- Middle Aged
- Trypanosoma cruzi
Keywords
- Chagas disease
- Chemokines
- Cohort
- Cytokines
- Immune biomarkers
A hexanucleotide repeat expansion on chromosome 9 open reading frame 72 (C9orf72) is associated with familial amyotrophic lateral sclerosis (ALS) and a subpopulation of patients with sporadic ALS and frontotemporal dementia. We used inducible pluripotent stem cells from neurotypic and C9orf72 (C9 ) ALS patients to derive neuronal progenitor cells. We demonstrated that C9 and neurotypic neuronal progenitor cells differentiate into neurons. The C9 neurons, however, spontaneously re-expressed cyclin D1 after 12 weeks, suggesting cell cycle re-engagement. Gene profiling revealed significant increases in senescence-associated genes in C9 neurons. Moreover, C9 neurons expressed high levels of mRNA for CXCL8, a chemokine overexpressed by senescent cells, while media from C9 neurons contained significant levels of CXCL8, CXCL1, IL13, IP10, CX3CL1, and reactive oxygen species, which are components of the senescence-associated secretory phenotype. Thus, re-engagement of cell cycle-associated proteins and a senescence-associated secretory phenotype could be fundamental components of neuronal dysfunction in ALS and frontotemporal dementia.
MeSH Terms
- Amyotrophic Lateral Sclerosis
- C9orf72 Protein
- Cell Cycle
- Cells, Cultured
- Cellular Senescence
- DNA Repeat Expansion
- Frontotemporal Dementia
- Gene Expression
- Gene Expression Regulation, Developmental
- Humans
- Induced Pluripotent Stem Cells
- Interleukin-8
- RNA, Messenger
- Stem Cells
Keywords
- Amyotrophic lateral sclerosis
- Cell cycle re-entry
- Frontotemporal dementia
- Senescence
- Senescence-associated secretory phenotype
To reveal age-related aqueous cytokine changes in human aqueous humor. Aqueous humor was collected from 12 young children (3-6.5 years old) and 71 healthy adults (22-106 years old) with cataract but without other systemic or ocular disorders. Levels of 22 cytokines, chemokines and vascular endothelial growth factor (VEGF) were measured and analyzed. The following proteins showed significant increase from childhood to adult: interferon-gamma (IFN-γ), interleukin (IL)-13, IL-6, IL-12(p70), IL-10, CCL2, CCL3, CCL4, CXCL8, CXCL9, CXCL10, IFN-α2 and VEGF (all [i]P[/i]<0.05). IFN-γ, IL-13, IL-12(p70), IL-10, CCL3, CXCL9 and VEGF also showed moderate strength age-related increase in the adult group ([i]r[/i]>0.5). The strength of correlation between aging and CCL4 were fair ([i]r[/i]=0.398). The concentrations of IL-2, IL-4, IL-5, IL-1β and TNF-α were low in both groups. From childhood to adult, the immunological milieu of the anterior chamber become more pro-inflammatory and pro-angiogenic. Such changes may represent the parainflammation state of the human eye.
Keywords
- aging
- aqueous humor
- cytokines
- macrophage
- parainflammation
- vascular endothelial growth factor
During immunosenescence many proinflammatory markers such as cytokines and chemokines are increased. This process called by Franceschi and colleagues as inflammaging is associated with chronic inflammation and the ethiology and pathophysiolgy of many ageing diseases as Alzheimer's and atherosclerosis. The knowledge of immune profile during ageing may provide some interventions that would improve the immune function in elderly and quality of life for old people. However, the identification of a group of potential biomarkers to monitor the ageing process is very difficult. In addition, most of the evidence evaluating immune biomarkers profile is based on data from older Caucasian adults. To our knowledge, no previous Latin American old population-based cohort has evaluated immunological parameters along the ageing process. The present work evaluated CXCL8, CXCL9, CXCL10, CCL2, CCL5, IL-1, IL-6, IL-12, TNF and IL-10 serum levels in 1494 older adults aged 60 to 95 from a population based ageing cohort in Brazil. Our data suggest that there is an increased positive predicted probability of participants to be a high producer of IL-6, CXCL8 and CXCL9. Moreover, results did not differ between men and women, except for CXCL10 that increased only in men. Results were not different in the adjusted model by many potential confounders, including African genomic ancestry. Together, these findings add novel insights about the immunologic aspects of ageing supported by a large population-based cohort study that provides evidences that corroborate with the inflammaging proposal and subsidize the establishment of biomarkers for monitoring the health status of aged population.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Biomarkers
- Brazil
- Chemokine CXCL10
- Chemokine CXCL9
- Cohort Studies
- Female
- Humans
- Immunosenescence
- Interleukin-6
- Interleukin-8
- Logistic Models
- Male
- Middle Aged
- Sex Factors
Keywords
- Ageing
- Biomarkers
- CXCL8
- CXCL9
- Gender
- IL-6
- Population-based cohort
Inflammation, particularly elevated IL-6 serum levels, has been associated with increased mortality risk, mostly in Caucasians. The influence of genetic ethno-racial background on this association is unknown. We examined associations between baseline serum levels of Interleukin-6 (IL-6) and other cytokines (IL1-2, TNF, IL-10, and IL1β) and chemokines (CCL2, CCL5, CXCL8, CXCL9 and CXCL10) with 15-year mortality in 1,191 admixed Brazilians aged 60years and over. Elevated IL6 level (but not other biomarkers) was associated with increased risk of deaths with fully adjusted hazard ratios of 1.51 (95% CI=1.15, 1.97), 1.54 (95% CI=1.20, 1.96) and 1.79 (95% CI=1.40, 2.29) for the 2nd, 3rd and the highest quartiles, respectively. Genomic African and Native American proportions did not modify the association (p>0.05). The discriminatory ability to predict death of a model based on IL-6 alone was similar as that of a comprehensive morbidity score (C statistics=0.59 and 0.60, respectively). The abilities of IL-6 and the morbidity score models to predict death remained stable for very long term after the baseline measurement. Our results indicate that genome-based African and Native American ancestries have no impact on the prognostic value of IL-6 for mortality.
MeSH Terms
- African Continental Ancestry Group
- Aged
- Aged, 80 and over
- Aging
- Biomarkers
- Brazil
- Cause of Death
- Chemokine CCL5
- Chemokine CXCL9
- Chemokines
- Female
- Follow-Up Studies
- Humans
- Indians, North American
- Interleukin-6
- Interleukin-8
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Predictive Value of Tests
- Prognosis
- Proportional Hazards Models
- Risk Assessment
- Risk Factors
- Time Factors
Keywords
- Admixed population
- Chemokines
- Cytokines
- Genomic ancestry
- Inflammatory markers
- Interleukin-6
- Mortality
Patients with pancreatic ductal adenocarcinoma (PDAC) commonly require chemotherapy because they frequently develop metastatic disease or locally advanced tumors. Gemcitabine, an analogue of cytosine arabinoside, is commonly used for PDAC treatment. We observed that gemcitabine induced senescence phenotypes characterized by enhanced senescence-associated β-galactosidase (SA β-Gal) staining and increased expression of senescence-associated molecules in two human pancreatic cancer cell lines, Miapaca-2 and Panc-1, which exhibit resistance to gemcitabine but not L3.pl cells with a high sensitivity to gemcitabine. Gemcitabine-induced cell senescence can be inhibited by reactive oxygen species inhibitor, N-acetyl cysteine. Although gemcitabine also enhanced CXCL8 expression, anti-CXCL8 antibody failed to reduce gemcitabine-induced increases in SA β-Gal-positive cell numbers. These observations would indicate that cell senescence can proceed independently of CXCL8 expression, a characteristic feature of senescence-associated secretion phenotype.
MeSH Terms
- Cellular Senescence
- Deoxycytidine
- Humans
- Pancreatic Neoplasms
Keywords
- CXCL8
- Gemcitabine
- Pancreatic cancer
- Senescence
Most infections occur in early life, prompting development of novel adjuvanted vaccines to protect newborns and infants. Several Toll-like receptor (TLR) agonists (TLRAs) are components of licensed vaccine formulations or are in development as candidate adjuvants. However, the type and magnitude of immune responses to TLRAs may vary with the TLR activated as well as age and geographic location. Most notably, in newborns, as compared to adults, the immune response to TLRAs is polarized with lower Th1 cytokine production and robust Th2 and anti-inflammatory cytokine production. The ontogeny of TLR-mediated cytokine responses in international cohorts has been reported, but no study has compared cytokine responses to TLRAs between U.S. neonates and infants at the age of 6months. Both are critical age groups for the currently pediatric vaccine schedule. In this study, we report quantitative differences in the production of a panel of 14 cytokines and chemokines after in vitro stimulation of newborn cord blood and infant and adult peripheral blood with agonists of TLR4, including monophosphoryl lipid A (MPLA) and glucopyranosyl lipid Adjuvant aqueous formulation (GLA-AF), as well as agonists of TLR7/8 (R848) and TLR9 (CpG). Both TLR4 agonists, MPLA and GLA-AF, induced greater concentrations of Th1 cytokines CXCL10, TNF and Interleukin (IL)-12p70 in infant and adult blood compared to newborn blood. All the tested TLRAs induced greater infant IFN-α2 production compared to newborn and adult blood. In contrast, CpG induced greater IFN-γ, IL-1β, IL-4, IL-12p40, IL-10 and CXCL8 in newborn than in infant and adult blood. Overall, to the extent that these in vitro studies mirror responses in vivo, our study demonstrates distinct age-specific effects of TLRAs that may inform their development as candidate adjuvants for early life vaccines.
MeSH Terms
- Adjuvants, Immunologic
- Adult
- Aging
- Cytokines
- Female
- Humans
- Infant
- Infant, Newborn
- Male
- Oligodeoxyribonucleotides
- Th1 Cells
- Th2 Cells
- Toll-Like Receptors
Keywords
- Adjuvant
- Immune ontogeny
- Infant
- Neonate
- Newborn
- Toll-like receptor (TLR)
It is believed that senescent cells contribute to the progression of primary and metastatic tumors, however, the exact mechanisms of this activity remain elusive. In this report we show that senescent human peritoneal mesothelial cells (HPMCs) alter the secretory profile of ovarian cancer cells (A2780, OVCAR-3, SKOV-3) by increasing the release of four angiogenic agents: CXCL1, CXCL8, HGF, and VEGF. Proliferation and migration of endothelial cells subjected to conditioned medium generated by: cancer cells modified by senescent HPMCs; cancer cells co-cultured with senescent HPMCs; and by early-passage HPMCs from aged donors, were markedly intensified. The same was the case for the vascularization, size and number of tumors that developed in the mouse peritoneum upon injection of ovarian cancer cells with senescent HPMCs. When the identified pro-angiogenic proteins were neutralized in conditioned medium from the cancer cells, both aspects of endothelial cell behavior intensified in vitro in response to senescent HPMCs were markedly reduced. The search for mediators of senescent HPMC activity using specific neutralizing antibodies and recombinant exogenous proteins showed that the intensified angiogenic potential of cancer cells was elicited by IL-6 and TGF-β1. At the transcriptional level, increased proliferation and migration of endothelial cells exposed to cancer cells modified by senescent HPMCs was regulated by HIF-1α, NF-κB/p50 and AP-1/c-Jun. Collectively, our findings indicate that senescent HPMCs may promote the progression of ovarian cancer cells by reprogramming their secretory phenotype towards increased production of pro-angiogenic agents and subsequent increase in the angiogenic capabilities of the vascular endothelium.
MeSH Terms
- Animals
- Cell Movement
- Cell Proliferation
- Cellular Senescence
- Disease Progression
- Epithelium
- Female
- Heterografts
- Humans
- Mice
- Mice, SCID
- Neovascularization, Pathologic
- Ovarian Neoplasms
- Peritoneum
- Phenotype
Keywords
- Angiogenesis
- Cellular senescence
- Mesothelial cells
- Ovarian cancer
- Peritoneal cavity
Gastrointestinal cancers metastasize into the peritoneal cavity in a process controlled by peritoneal mesothelial cells (HPMCs). In this paper we examined if senescent HPMCs can intensify the progression of colorectal (SW480) and pancreatic (PSN-1) cancers in vitro and in vivo. Experiments showed that senescent HPMCs stimulate proliferation, migration and invasion of SW480 cells, and migration of PSN-1 cells. When SW480 cells were injected i.p. with senescent HPMCs, the dynamics of tumor formation and vascularization were increased. When xenografts were generated using PSN-1 cells, senescent HPMCs failed to favor their growth. SW480 cells subjected to senescent HPMCs displayed up-regulated expression of transcripts for various pro-cancerogenic agents as well as increased secretion of their products. Moreover, they underwent an epithelial-mesenchymal transition in the Smad 2/3-Snail1-related pathway. The search for mediators of senescent HPMC activity showed that increased SW480 cell proliferation was stimulated by IL-6, migration by CXCL8 and CCL2, invasion by IL-6, MMP-3 and uPA, and epithelial-mesenchymal transition by TGF-β1. Secretion of these agents by senescent HPMCs was increased in an NF-κB- and p38 MAPK-dependent mechanism. Collectively, our findings indicate that in the peritoneum senescent HPMCs may create a metastatic niche in which critical aspects of cancer progression become intensified.
MeSH Terms
- Animals
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Cellular Senescence
- Colorectal Neoplasms
- Epithelial-Mesenchymal Transition
- Gene Expression Regulation, Neoplastic
- Humans
- Mice, SCID
- Neoplasm Invasiveness
- Pancreatic Neoplasms
- Paracrine Communication
- Peritoneal Neoplasms
- Peritoneum
- Signal Transduction
- Time Factors
- Tumor Microenvironment
Keywords
- cellular senescence
- gastrointestinal cancers
- mesothelial cells
- mice xenografts
- peritoneal cavity
Osteoarthritis (OA) is a major cause of morbidity and incapacity in the elderly. This study evaluates serum levels of the chemokines CCL2, CXCL8, CXCL9, and CXCL10 in 16 patients with primary OA of the knees, and investigates how treatment with hydroxychloroquine (HCQ) for 4 months affects these chemokine levels. Thirteen elderly patients received a placebo. Healthy control groups consisted of 10 elderly individuals (age > 60 years) with no clinical or radiological evidence of OA (CT-O), and 10 young adult individuals, (CT-Y group, age < 40 years). The CT-Y group presented lower levels of all chemokines studied, in comparison to the other groups. HCQ treatment did not alter the serum levels of CCL2 (P = 0.80), CXCL8 (P = 0.76), CXCL9 (P = 0.95) and CXCL10 (P = 0.74) in OA patients. Hydroxychloroquine treatment did not alter the serum levels of CCL2, CXCL8, CXCL9 or CXCL10 in patients with OA of the knees, although increased serum levels correlated with aging for all subjects, including controls.
MeSH Terms
- Age Factors
- Aged
- Aging
- Antirheumatic Agents
- Biomarkers
- Case-Control Studies
- Chemokine CCL2
- Chemokine CXCL10
- Chemokine CXCL9
- Female
- Humans
- Hydroxychloroquine
- Interleukin-8
- Male
- Middle Aged
- Osteoarthritis, Knee
- Time Factors
- Treatment Outcome
- Up-Regulation
Keywords
- aging
- arthritis
- chemokines
- hydroxychloroquine
- pain
Neutrophils are pivotal effector cells of innate immunity representing the first line of defense against aggression. They are the first cells to arrive at the site of the aggression, where they can directly eliminate the invading microorganisms. Their activation and recruitment into peripheral tissues is indispensable for host defense. With aging, there are alterations of the receptor by driven functions of human neutrophils as a decrease in the functional changes in signaling elicited by specific receptors, as CXCR1. We investigated the activation of neutrophils from elderly after the cells were cultivated with CXCL8. Although, CXCL8 induced elastase (ELA) secretion, data showed neither myeloperoxidase (MPO) activity nor production of IL-6, IL-10, GM-CSF by neutrophils from elderly compared with young individuals. On the other hand, in the presence of only LPS or LPS associated with CXCL8 neutrophils from elderly individuals, there were significant levels of IL-6, IL-10, GM-CSF but not MPO. These results indicate that neutrophils from elderly do not respond to CXCL8 stimulus, but they are activated by LPS to produce cytokines. However, MPO activity from elderly individuals was not different in the presence or absence of LPS and CXCL8.
MeSH Terms
- Adult
- Aged
- Aging
- Humans
- Interleukin-8
- Middle Aged
- Neutrophil Activation
- Neutrophils
- Pancreatic Elastase
- Peroxidase
- Young Adult
Little is known about biochemical mediators that correlate with the initiation and progression of knee osteoarthritis (OA). We therefore valuated the roles of cytokines and metalloenzymes in knee OA in relation to OA grading, age, and BMI. A multiplex ELISA-based immunoassay (Luminex technology) was used to measure biochemical mediators in the synovial fluid (SF) of 82 patients undergoing knee surgery. All patients were classified according to age, BMI, and OA grade. 24 patients had no signs of OA (knee reconstruction surgeries). The mediators that were tested for included interleukins (IL-1Ra, IL-6, IL-7, and IL-18), chemokines (CCL2 (MCP-1), CCL3 (MIP-1a), and CXCL8 (IL-8)), growth factors (HGF and VEGF), and matrix metalloproteinases (MMP-1, MMP-2, MMP-9, and MMP-13). There was a correlation between IL-7 levels in SF and age (p < 0.01). The 11 highest IL-7 levels were seen in patients who were aged between 59 and 72 but had different OA grades. In contrast, all patients who had severe OA in all 3 knee compartments (pan-OA) had only low or medium IL-7 levels. There was a negative correlation between MMP-1 levels in synovial fluid and grade of OA (p < 0.001). Correlation studies between pairs of mediators revealed two groups of mediators that are important in OA progression, dominated by MCP-1 and IL-1Ra. IL-7 levels in SF are elevated in elderly people suffering from OA of different grades, but they are depressed in patients with severe 3-compartment OA, possibly due to widely impaired chondrocytes embedded in the affected cartilage tissue. The observed decrease in MMP-1 levels in SF, which is dependent on the severity of OA, may be caused by deterioration of superficial cartilage layers during progression of OA.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Biomarkers
- Cellular Senescence
- Chemokine CCL2
- Chondrocytes
- Disease Progression
- Enzyme-Linked Immunosorbent Assay
- Female
- Humans
- Immunoassay
- Interleukin 1 Receptor Antagonist Protein
- Interleukin-18
- Interleukin-6
- Interleukin-7
- Male
- Matrix Metalloproteinase 1
- Matrix Metalloproteinases
- Middle Aged
- Osteoarthritis
- Severity of Illness Index
- Synovial Fluid
- Vascular Endothelial Growth Factor A
Circulating levels of cytokines are deeply influenced by aging, and few data about serum chemokines are available. The aim of this study was to evaluate the influence of aging on circulating CXCL10. One hundred forty healthy subjects (70 males and 70 females), 10-79 years of age, underwent fasting plasma glucose, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, and CXCL8 serum assay. Thyroid hormone testing for thyroid-stimulating hormone (TSH), antithyroglobulin (AbTg), and antithyroperoxidase (AbTPO) autoantibodies and thyroid ultrasonography were performed in all subjects to exclude the presence of clinical or subclinical thyroid disease. Serum CXCL10 levels were assayed in all subjects and found to be increased in 14 of 70 females (20%) and in 4 of 70 males (5.7%) (p = 0.01). In a multiple linear regression model including age, body mass index (BMI), systolic and diastolic blood pressure, glycemia, total cholesterol, HDL, LDL, triglycerides, TSH, AbTPO, AbTg, and CXCL8, only age was significantly related to CXCL10 [C.R. 1.30 (0.28-2.33), p = 0.001]. No relationship was present between CXCL8 serum levels and age, suggesting a specificity of CXCL10 elevation as a function of age. Results of this study, performed in healthy subjects on an age gradient, demonstrate an increase in serum CXCL10 with advancing age overall in females, supporting the hypothesis of enhanced Th1 immune responses in aging.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- Chemokine CXCL10
- Chemokines, CXC
- Child
- Female
- Humans
- Male
- Middle Aged
- Thyroid Diseases
Increasing evidence suggests that the chemokine interleukin (IL)-8/CXCL8 plays important roles in CNS development, neuronal survival, modulation of excitability, and neuroimmune response. Recently, we have shown that CXCL8 can acutely modulate ion channel activity in septal neurons expressing receptors CXCR1 and/or CXCR2. This was a surprising finding, insofar as CXCR1 expression had not been described for the mammalian brain. Here we investigated whether CXCR1 transcripts are present in other brain regions, whether they are expressed at the single-cell level in molecularly identified neurons and astrocytes, and how they are regulated during early postnatal development. In addition, possible cellular colocalization of CXCR1 and CXCR2 transcripts was examined. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed that CXCR1 mRNAs were expressed in the septum, striatum, hippocampus, cerebellum, and cortex (temporoparietal and entorhinal) at different levels and appeared to be regulated independently from CXCR2 during development. By using RT multiplex PCR on acutely dissociated cells from these brain regions, we show that CXCR1 transcripts were expressed in 83% of 84 sampled neurons displaying cholinergic (choline acetyltransferase mRNAs), gamma-aminobutyric acidergic (glutamic acid decarboxylases 65 and 67 mRNAs), or glutamatergic (vesicular glutamate transporters 1 and 2 mRNAs) phenotypes. CXCR1 and CXCR2 transcripts were colocalized in 45% of neurons sampled and also were present in some glial fibrillary acidic protein mRNA-expressing astrocytes. This is the first study to demonstrate the widespread expression of CXCR1 transcripts in the brain and suggests that CXCR1 may have hitherto unsuspected roles in neuromodulation and inflammation.
MeSH Terms
- Acetylcholine
- Aging
- Animals
- Animals, Newborn
- Astrocytes
- Brain
- Cell Line
- Cell Separation
- Female
- Glutamic Acid
- Neurons
- RNA, Messenger
- Rats
- Rats, Sprague-Dawley
- Receptors, Interleukin-8A
- Receptors, Interleukin-8B
- gamma-Aminobutyric Acid