CXCL9
C-X-C motif chemokine 9 precursor (Gamma-interferon-induced monokine) (Monokine induced by interferon-gamma) (HuMIG) (MIG) (Small-inducible cytokine B9) [CMK] [MIG] [SCYB9]
Publications[править]
Chronic graft-vs-host disease (cGVHD) is a multifactorial inflammatory disease that affects patients undergoing hematopoietic stem cell transplantation. Multiple organs, including the lacrimal glands (LGs), are negatively affected by cGVHD and lose function due to the resultant fibrosis. An abnormal immune response is thought to be a major factor in the development of chronic ocular GVHD, which is currently treated primarily with immunosuppressive therapies. However, all the treatments yield unsatisfactory outcomes, and additional treatment strategies are needed. To meet this unmet medical need, we aimed to elucidate an additional pathway of chronic ocular GVHD. Our findings suggest a potential association between chronic ocular GVHD pathogenesis and stress-induced cellular senescence through the senescence-associated secretory phenotype (SASP). Senescent cells produce cytokines and chemokines, such as IL-6 and CXCL9. Indeed, senescent cell accumulation was presumably associated with cGVHD development in LGs, as evidenced by the improvement in LGs after the selective elimination of senescent cells (senolysis) with ABT-263. Results in the sclerodermatous cGVHD mouse model suggest that inhibiting the major components of the SASP, including IL-6 and CXCL9, with senolytics is a potential novel strategy for treating cGVHD-affected LGs. Taken together, our results indicate a potential association between the SASP and cGVHD development in LGs and suggest that targeted senolytic treatment may be a new therapeutic option for this disease.
Keywords
- chronic ocular graft-vs-host disease
- lacrimal glands
- senescence-associated secretory phenotype
- senolytic treatment
- stress-induced senescence
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
Analyze whether inflammatory markers are associated with falls among older adults living in Bambuí. Study that analyzed baseline data from a Bambuí Cohort Study of Aging, involving 1,250 participants. Data about falls were collected from previous 12 months, classified as single or multiple occurrence and severity (participant seeking health services). Information about sociodemographic characteristics, health behaviors and health condition was also collected and used as confounding factors. The exposures of interest included interleukins (IL-1β, IL-6, IL-8, IL-10, IL-12), tumor necrosis factor (TNF), ultra-sensitive C-reactive protein (us-CRP) and chemokines (CXCL9, CCL5, CCL10, MCP1). Data were processed through logistic regression, obtaining odds ratio and 95% confidence interval (95%CI). The prevalence of falls was 27.1%; 40.1% of the older adults reported multiple falls and 33.3% sought health services. After adjustments, the following elevated levels were associated with falls: us-CRP (OR = 1.46, 95%CI 1.04-2.03), CCL5 (OR = 1.38, 95%CI 1.01-1.90) and CXCL9 (OR = 1.43, 95%CI 1.02-2.02). An association was observed between the number of elevated markers and the occurrence of falls: two (OR = 1.47, 95%CI 1.02-2.12) and three (OR = 2.08, 95%CI 1.12-3.87) elevated biomarkers indicated fall probability of 32.0% and 39.4%, respectively. Elevated levels of us-CRP, CCL5 and CXCL9, which were associated with falls, may contribute to a proper understanding of the mechanism associated with the occurrence of falls among older people.
MeSH Terms
- Accidental Falls
- Aged
- Aging
- Biomarkers
- Body Mass Index
- Brazil
- Chemokines
- Educational Status
- Female
- Humans
- Interleukins
- Male
- Middle Aged
- Nutritional Status
- Polymerase Chain Reaction
- Prospective Studies
- Risk Factors
- Tumor Necrosis Factor-alpha
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
Natural killer (NK) cells play an important role in controlling several viral diseases. Our previous studies demonstrated an age-dependent susceptibility to mousepox due to defective NK cell responses and trafficking. However, the mechanisms that underlie the age-related impairment in NK cell migration have yet to be identified. In the present study, we demonstrated that after influenza A virus (IAV) infection, NK cells from aged mice (17-19months old) failed to accumulate in draining lymph node (D-LN). We found that both environmental and intrinsic factors played roles for this defect. After infection, increase of chemokine transcripts, especially CXCL9, 10 and 11, which are important for NK cells homing to D-LN, was significantly lower in the D-LN of aged mice compared with those of young mice. Further, the expression levels of β2-integrins and β-actins, which play critical roles in NK cells homing to D-LN failed to be up-regulated in NK cells from aged mice. Finally, actin polymerization rates in NK cells from aged mice were also delayed compared to that of the young mice after IAV infection. Taken together, our data indicate that bi-directional factors play essential roles in the defective NK cell trafficking to the D-LN in the aged mice after IAV infection.
MeSH Terms
- Actinin
- Aging
- Analysis of Variance
- Animals
- CD18 Antigens
- Cell Movement
- Chemokines
- Female
- Humans
- Influenza, Human
- Killer Cells, Natural
- Lymph Nodes
- Mice, Inbred C57BL
- Receptors, Immunologic
Keywords
- Cell migration
- Draining lymph node
- IAV infection
- Immunosenescence
- Infectious disease
- NK cells
Cardiovascular disease (CVD) is the leading cause of death in the industrialized world. Aging is the most predictive risk factor for CVD and is associated with arterial inflammation which contributes to increased CVD risk. Although age-related arterial inflammation has been described in both humans and animals, only a limited number of inflammatory mediators, cytokines and chemokines have been identified. In this investigation we sought to determine whether lifespan extending interventions, including crowded litter early life nutrient deprivation (CL), traditional lifelong caloric restriction (CR) and lifelong Rapamycin treatment (Rap) would attenuate age-related arterial inflammation using multi analyte profiling. Aortas from Young (4-6months), Old (22months), Old CL, Old CR and Old Rap mice were homogenized and cytokine concentrations were assessed using Luminex Multi Analyte Profiling. Chemokines involved in immune cell recruitment, such as CCL2, CXCL9, CXCL10, GMCSF and MCSF, were increased in Old vs. Young (p<0.05). The age-related increase of CXCL10 was prevented by CR (p<0.05 vs. Old). MSCF concentrations were lower in aortas of Rap treated mice (p<0.05 vs. Old). Interleukins (IL), IL-1α, IL-1β and IL-10, were also greater in Old vs. Young mice (p<0.05). These data demonstrate selected lifespan extending interventions can prevent or limit age-related increases in selected aortic chemokines.
MeSH Terms
- Aging
- Animals
- Arteries
- Caloric Restriction
- Cardiovascular Diseases
- Chemokine CCL2
- Chemokine CCL4
- Chemokine CXCL10
- Chemokines
- Cytokines
- Early Medical Intervention
- Interleukin-10
- Interleukin-1beta
- Interleukins
- Macrophage Colony-Stimulating Factor
- Male
- Mice
- Sirolimus
Keywords
- Aorta
- Caloric restriction
- Chemokine
- Cytokine
- Interleukin
- Rapamycin
Thinning of the RPE and the underlying vascular layer, the choroid, is observed with age in many human eye disorders. The reasons for this thinning are ill-defined. Here, we highlight the possible role of T lymphocyte recruitment in choroidoretinal thinning in aged and light-challenged mice. In age and light challenge models, we measured chemokine concentrations using enzyme-linked immunosorbent assay and used flow cytometry to characterize lymphocyte populations. We quantified thinning in eye immunosections and [[RPE65]] expression using quantitative PCR. Age and light challenge led to increased levels of the lymphotactic protein CXCL10 alone (aging) or in conjunction with CXCL9 (light challenge). Increased numbers of CD3 T lymphocytes, most of them CD8 cytotoxic T lymphocytes, were also observed in the choroid and retina of old mice and following light challenge. Influx of T lymphocytes was associated with RPE and choroidal thinning and diminished expression of [[RPE65]] mRNA, an essential enzyme of the visual cycle. The observations from this study suggest that cytotoxic CD8( ) T lymphocytes might participate in choroidal and RPE degeneration and that modulation of T lymphocyte recruitment might be a novel strategy to reduce choroidoretinal dysfunctions observed with age and following photo-oxidative stress.
MeSH Terms
- Aging
- Animals
- Cell Movement
- Chemokine CXCL10
- Chemokine CXCL9
- Choroid
- Gene Expression Regulation
- Humans
- Light
- Mice
- Mice, Inbred C57BL
- Oxidative Stress
- Photochemical Processes
- RNA, Messenger
- Retinal Pigment Epithelium
- T-Lymphocytes, Cytotoxic
- cis-trans-Isomerases
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
Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by unresolved inflammation and tissue repair pathologies triggered by repeated organic dust exposure. The aim of the study was to investigate changes in levels of the cathelicidin related antimicrobial peptide (CRAMP), laminin (LAM-A1), selected Toll-like receptors (TLR) and chemokines in experimental HP in mice. Three and 18-month-old female C57BL/6J mice underwent inhalations of the saline extract of Pantoea agglomerans cells, Gram-negative bacterium common in organic dust and known for its pathogenic impact. The inhalations were repeated daily (28 days). ELISA was used for measuring in lung tissue homogenates concentration of CRAMP, LAM-A1, TLR2, TLR4, TLR8, CXCL9 (chemokine [C-X-C motif] ligand) and CXCL10. Levels of TLR2, TLR4 and CXCL9 were significantly higher in both young and old mice lungs already after 7 days of inhalations, while significant increase of LAM-A1 and CXCL10 was noted after 28 days, compared to untreated samples. TLR8 level was significantly augmented only in young mice. Only CRAMP level significantly declined. Significantly higher TLR8 and CXCL9 concentration in untreated samples were noted in old animals compared to young ones. Significant alterations of the examined factors levels indicate their role in HP pathogenesis.
MeSH Terms
- Administration, Inhalation
- Aerosols
- Aging
- Alveolitis, Extrinsic Allergic
- Animals
- Antimicrobial Cationic Peptides
- Cathelicidins
- Cell Extracts
- Chemokine CXCL10
- Chemokine CXCL9
- Disease Models, Animal
- Female
- Laminin
- Mice
- Mice, Inbred C57BL
- Pantoea
- Protein Precursors
- Toll-Like Receptors
Keywords
- Antimicrobial peptide
- Hypersensitivity pneumonitis
- Mice model
- Modèle murin
- Pantoea agglomerans
- Peptides antimicrobiens
- Pneumopathie d’hypersensibilité
- Récepteurs de type Toll
- Toll-like receptors
Aging is often accompanied by increased levels of inflammatory molecules in the organism, but age-related changes in the brain response to inflammatory challenges still require clarification. We here investigated in mice whether cytokine signaling and T-cell neuroinvasion undergo age-related changes. We first analyzed the expression of molecules involved in T-cell infiltration and cytokine signaling regulation in the septum and hippocampus of 2-3 months and 20- to 24-month-old mice at 4h after intracerebroventricular injections of tumor necrosis factor (TNF)-alpha or interferon-gammaversus saline injections. Transcripts of the chemokine CXCL9, intercellular adhesion molecule (ICAM)-1 and suppressor of cytokine signaling molecules (SOCS) 1 and 3 were increased in both age groups after cytokine injection; microglia-derived matrix metalloproteinase (MMP) 12 mRNA was induced in old mice also after control saline injections. Age-related changes in ICAM-1 protein expression and T-cell infiltration were then analyzed in mice of 3-4, 8-9 and 15-16 months at 48h after TNF-alpha injections. ICAM-1 immunoreactivity, and Western blotting in striatum, septum, hippocampus and hypothalamus showed progressive age-related enhancement of TNF-alpha-elicited ICAM-1 upregulation. Double immunofluorescence revealed ICAM-1 expression in microglia and astrocytic processes. CD3( ), CD4( ) and CD8( ) T-cells exhibited progressive age-related increases in brain parenchyma and choroid plexus after cytokine exposure. The findings indicate that the brain responses to inflammatory challenges are not only preserved with advancing age, but also include gradual amplification of ICAM-1 expression and T-cell recruitment. The data highlight molecular and cellular correlates of age-related increase of brain sensitivity to inflammatory stimuli, which could be involved in altered brain vulnerability during aging.
MeSH Terms
- Aging
- Animals
- Blotting, Western
- Brain
- Cytokines
- Data Interpretation, Statistical
- Immunohistochemistry
- Inflammation
- Injections, Intraventricular
- Intercellular Adhesion Molecule-1
- Male
- Mice
- Mice, Inbred C57BL
- RNA
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
- T-Lymphocytes
- Transcription, Genetic
- Tumor Necrosis Factor-alpha
Cytokine and chemokine responses during anamnestic type-1 and type-2 lung granuloma formation were evaluated in mice at 6,12,18 and 24-months of age. Lesions were induced by embolizing Sepharose beads coupled to Mycobacterium bovis purified protein derivative or soluble Schistosoma mansoni egg antigens. Type-1 inflammation was reduced by 18 months, whereas type-2 granulomas not until 24 months of age. In type-1 draining lymph nodes cultures, interferon-gamma (IFNgamma) declined to a nadir by 18, and then partly recovered at 24 months. In contrast, IL-4 was not significantly impaired in type-2 cultures until 24 months. Type-1 and 2 node cultures also displayed decreased IL-13, but paradoxically enhanced IL-5 production at 24 months. Chemokine transcripts in granulomatous lungs displayed age-related alterations. In the type-1 response, CXCL9 (monokine-induced by IFNgamma) declined with age then partly recovered at 24 months parallelling lymph node IFNgamma levels. Transcripts for MIP-2/CXCL2, IP-10/CXCL10, MCP-1/CCL2, and MCP-5/CCL12 increased at 24 months. In the type-2 response MCP-1/CCL2, MCP-3/CCL7, MCP-5/CCL12 and TARC/CCL17 collapsed at 24 months paralleling local IL-4 transcript levels, yet some chemokine transcripts such as KC/CXCL1 and eotaxin/CCL11 were unaffected. These findings suggest that cytokine and chemokine responses degrade differentially with age shifting Th1/Th2 crossregulatory pressures and local expression of chemokines.
MeSH Terms
- Aging
- Animals
- Chemokines
- Cytokines
- Granuloma, Respiratory Tract
- Lung
- Lymph Nodes
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mycobacterium bovis
- Schistosoma mansoni
- Schistosomiasis mansoni
- Tuberculosis