interleukin-8 and Sjogren-s-Syndrome

Topics: Arthritis, Rheumatoid; Behcet Syndrome; Biomarkers; Bronchitis; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-10; Interleukin-7; Interleukin-8; Interleukin-9; Lupus Erythematosus, Systemic; Psoriasis; Reagent Kits, Diagnostic; Sjogren's Syndrome

To evaluate the expression of IL8/CXCL8 cytokine and its receptor CXCR1 in tear film and ocular surface of patients with ocular mucous membrane pemphigoid (oMMP).. Ten patients with oMMP in the quiescent phase, 20 patients with primary Sjogren syndrome (pSS) and 13 age- and sex-matched healthy controls (HCs) were included in this study. All patients undergone complete eye examination including lacrimal function tests and ocular surface staining assessed by ocular staining score. Ocular mucous membrane pemphigoid (oMMP) staging according to Mondino classification and dry eye severity grade according to Dry Eye Workshop 2007 classification were recorded. Tear samples and conjunctival epithelium were collected. IL-8 tear concentration was measured by enzyme-linked immunosorbent assay, and conjunctival IL8 was analysed by Western blot; conjunctival expression of CXCR1 was evaluated by immunohistochemistry. Il-8 and CXCR1 expression in oMMP patients were compared with HCand pSS patients and correlated with ocular clinical findings.. Tear levels of IL-8 were significantly increased in patients with oMMP (260.1 ± 70 pg/ml) when compared to both HCs (98.5 ± 71.35 pg/ml; p = 0.001) and patients with pSS (96.3 ± 87.5 pg/ml; p = 0.001). Conjunctival expression of IL8 and CXCR1 was significantly increased in oMMP patients when compared to both healthy subjects and pSS patients.. The significant increase of tear and conjunctival IL8 and CXCR1 levels in patients with oMMP when compared to healthy subjects and patients with Sjogren syndrome suggests that changes of IL8 pathway are specific of oMMP and may represent a potential biomarker of the disease and/or therapeutic target.

Topics: Adult; Aged; Biomarkers; Blotting, Western; Conjunctiva; Enzyme-Linked Immunosorbent Assay; Epithelium; Female; Humans; Immunohistochemistry; Interleukin-8; Male; Middle Aged; Pemphigoid, Benign Mucous Membrane; Receptors, Interleukin-8A; Sjogren's Syndrome; Tears

Small airway disease and chronic obstructive pulmonary disease are common in primary Sjögren's syndrome (pSS). However, the underlying inflammatory mechanisms behind pSS-associated airway disease have not been studied in detail. We therefore wanted to study cytokine and leucocyte levels in induced sputum in never-smoking patients with pSS.. Induced sputum cytokines and leucocytes were assessed in 20 never-smoking patients with pSS and 19 age- and gender-matched population-based controls. In addition, pulmonary function, disease activity, respiratory symptoms, and inflammatory and serological features of pSS were assessed.. B-cell activating factor (BAFF), interleukin-6 (IL-6) and IL-8 were significantly increased in induced sputum in pSS patients compared to population-based controls, while IL-1β, interferon-α, and tumour necrosis factor-α levels and leucocytes were not. The proportion of lymphocytes and BAFF levels in induced sputum correlated significantly in pSS patients. However, cytokine levels in induced sputum were not associated with pulmonary function tests, disease activity, respiratory symptoms, or serological features of pSS.. The increase in BAFF, IL-6, and IL-8 in induced sputum suggests a specific ongoing inflammatory disease process in the airways in pSS patients. Its association with pSS-associated airway disease needs to be further examined in future larger studies.

Topics: Adult; Aged; Aged, 80 and over; B-Cell Activating Factor; Case-Control Studies; Female; Humans; Interleukin-6; Interleukin-8; Leukocytes; Male; Middle Aged; Sjogren's Syndrome; Sputum

To evaluate the response of the lacrimal function unit in Sjögren syndrome (SS)-associated dry eye patients exposed to 2 simulated daily life environmental conditions.. Prospective crossover pilot study.. Fourteen female SS dry eye patients were exposed for 2 hours to a controlled normal condition (23 C, 45% relative humidity, and air flow 0.10 m/s) and a controlled adverse condition that simulates desiccating stress (23 C, 5% relative humidity, and air flow 0.10 m/s). The following dry eye tests were performed before and after the exposure: tear osmolarity, phenol red thread test, conjunctival hyperemia, fluorescein tear break-up time, corneal fluorescein staining, conjunctival lissamine green staining, and Schirmer test. Levels of 16 molecules were analyzed in tears by multiplex immunobead analysis.. Clinical evaluation showed lacrimal functional unit impairment after the desiccating stress: significantly increased tear osmolarity (315.7 ± 3.0 vs 327.7 ± 5.1 mOsm/L, P = .03), conjunctival hyperemia (1.3 ± 0.1 vs 1.6 ± 0.1, P = .05), and corneal staining in temporal (3.5 ± 0.5 vs 4.7 ± 0.4, P = .01) and nasal (3.6 ± 0.5 vs 4.5 ± 0.5, P = .04) areas. Tear concentrations increased for interleukin-1 receptor antagonist (16 557.1 ± 4047.8 vs 31 895.3 ± 5916.5 pg/mL, P = .01), interleukin-6 (63.8 ± 20.2 vs 111.5 ± 29.6 pg/mL, P = .02), interleukin-8 (2196.1 ± 737.9 vs 3753.2 ± 1106.0 pg/mL, P = .03), and matrix metalloproteinase-9 (101 515.6 ± 37 088.4 vs 145 867.1 ± 41 651.5 pg/mL, P = .03). After the simulated normal condition, only a significant increase in nasal corneal staining (2.9 ± 0.5 vs 3.6 ± 0.5, P = .03) was observed.. Even a short exposure to a desiccating environment can produce a significant deterioration of the lacrimal function unit in female SS dry eye patients. The often unnoticed exposure to these conditions during daily life may increase inflammatory activity rapidly, triggering an ocular surface deterioration.

Topics: Adult; Aged; Cross-Over Studies; Dry Eye Syndromes; Environment, Controlled; Eye Proteins; Female; Fluorophotometry; Humans; Humidity; Interleukin 1 Receptor Antagonist Protein; Interleukin-6; Interleukin-8; Lacrimal Apparatus Diseases; Matrix Metalloproteinase 9; Middle Aged; Osmolar Concentration; Pilot Projects; Prospective Studies; Sjogren's Syndrome; Staining and Labeling; Stress, Physiological; Tears

Sjögren's syndrome antigen B is expressed in the nucleus and surface membrane of human polymorphonuclear neutrophils and is released after cell death. However, its biological role is not clear. This study is aimed to investigate the effect of Sjögren's syndrome antigen B on human polymorphonuclear neutrophils.. Human recombinant Sjögren's syndrome antigen B (rSSB) purified from E. coli was incubated with human polymorphonuclear neutrophils as well as retinoid acid-induced granulocytic differentiated HL-60 cells, HL-60 (RA). Interleukin (IL)-8 protein production and mRNA expressions were measured by enzyme-linked immunosorbent assay and quantitative-polymerase chain reaction, respectively. Uptake of fluorescein isothiocyanate (FITC)-rSSB was assessed by flow cytometry and fluorescence microscopy. Moreover, mitogen-activated protein kinase (MAPK) pathways and nuclear factor-kappaB activation were investigated.. Human rSSB stimulated IL-8 production from normal human neutrophils and HL-60 (RA) cells in a time- and dose-dependent manner. This IL-8-stimulated activity was blocked by chloroquine and NH4Cl, indicating that endosomal acidification is important for this effect. We found rSSB activated both MAPK pathway and nuclear factor-kappaB signaling to transcribe the IL-8 gene expression of cells. Furthermore, tumor necrosis factor-α exerted an additive effect and rSSB-anti-SSB immune complex exhibited a synergistic effect on rSSB-induced IL-8 production.. Sjögren's syndrome antigen B might act as an endogenous danger molecule to enhance IL-8 gene expression in human polymorphonuclear neutrophils.

Topics: Ammonium Chloride; Autoantigens; Chloroquine; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; HL-60 Cells; Humans; Interleukin-8; MAP Kinase Signaling System; Microscopy, Fluorescence; Neutrophils; Real-Time Polymerase Chain Reaction; Recombinant Proteins; Ribonucleoproteins; Sjogren's Syndrome; SS-B Antigen; Tumor Necrosis Factor-alpha

The regenerating gene (Reg) was isolated originally as a gene specifically over-expressed in regenerating pancreatic islets and constitute a growth factor family. Reg gene product (Reg) is important in the pathophysiology of various human inflammatory diseases. Recently, the possible involvement of human REG in the regeneration of salivary ductal epithelial cells of patients with primary Sjögren's syndrome (SS) was reported. However, the expression of the REG family genes in minor salivary glands (MSG) and the occurrence of anti-REG Iα autoantibodies in SS patients were obscured. In this study, we examined the expression of REG family genes in the MSG of SS and screened anti-REG Iα autoantibodies in SS. The mRNA levels of REG family genes in MSG were quantified using real-time reverse transcription-polymerase chain reaction (RT-PCR) and REG Iα expression in the MSG was analysed by immunohistochemistry. The mRNA level of REG Iα in the MSG of SS patients was significantly higher than that of control. REG Iα protein was expressed highly in SS ductal epithelial cells. Anti-REG Iα autoantibodies in the sera were found in 11% of SS. All the MSG in the anti-REG Iα autoantibody-positive group showed REG Iα expression, whereas only 40% showed REG Iα expression in the anti-REG Iα autoantibody-negative group. The anti-REG Iα autoantibody-positive group showed significantly lower saliva secretion and a higher ratio of grade 4 (by Rubin-Holt) in sialography. These data suggest strongly that autoimmunity to REG Iα might play a role in the degeneration of MSG ductal epithelial cells in primary SS.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Autoimmune Diseases; Child; Female; Humans; Interleukin-6; Interleukin-8; Lithostathine; Male; Middle Aged; Salivary Glands, Minor; Sjogren's Syndrome; Young Adult

We encountered a neonatal patient with hemophagocytic lymphohistiocytosis (HLH) whose mother was positive for anti-Ro/SSA and anti-La/SSB antibodies. Complete atrioventricular block was found in a male patient at 29 weeks of gestation. The patient was born at 40 weeks of gestation. He showed severe circulatory disturbance at 22 h after the birth, and he also had elevated serum levels of aspartate aminotransferase (1027 IU l(-1)), alanine aminotransferase (121 IU l(-1)), lactic dehydrogenase (3490 IU l(-1)), ferritin (9769.7 ng ml(-1)) and soluble interleukin-2 (IL-2) receptor (3230 U ml(-1)). We could not find any known HLH genetic abnormality in the patient, but he fulfilled seven of the eight criteria for HLH. Serum levels of IL-6 and IL-8 had been already elevated in his cord blood, and serum levels of granulocyte-macrophage colony-stimulating factor and IL-8 were significantly increased on the second day of life. His symptoms regressed with the administration of hydrocortisone. We presumed that transplacental transfer of maternal antibodies could be related to the occurrence of HLH.

Topics: Antibodies, Antinuclear; Atrioventricular Block; Autoimmunity; Chemokines; Cytokines; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Lymphohistiocytosis, Hemophagocytic; Male; Sjogren's Syndrome

The conventional H(1) and H(2) histamine receptors have >10,000-fold lower avidity for histamine than H(4) histamine receptor, which has been implicated in autoimmune diseases. This study was undertaken to compare H(4) histamine receptor levels in the salivary glands (SGs) of healthy controls with those in the SGs of patients with primary Sjögren's syndrome (SS).. H(4) histamine receptor messenger RNA (mRNA) was analyzed using real-time quantitative polymerase chain reaction, and the receptor protein was examined using immunostaining. Effects of the H(4) histamine receptor agonist ST-1006 on cytokine synthesis by human SG (HSG) cells were analyzed using xMAP technology and enzyme-linked immunosorbent assay.. Healthy SGs contained H(4) histamine receptor mRNA. The receptor protein was localized to the acinar and ductal epithelial cells. H(4) histamine receptor agonist stimulated HSG cells to produce the cytokines interleukin-8 and vascular endothelial growth factor. SS patients had low H(4) histamine receptor levels.. H(1) and H(2) histamine receptor antagonists are not effective in the treatment of autoimmune diseases. However, such antagonists do not affect the newly discovered H(4) histamine receptor. Dendritic cells and lymphocytes are nonprofessional histamine-producing cells, which produce histamine at 100-1,000-fold lower rates than mast cells do. Saliva contains only 0.31-12.4 ng/ml histamine, which is too low to stimulate H(1) or H(2) histamine receptor, but stimulates H(4) histamine receptor half maximally. Our findings show that H(4) histamine receptor is strongly expressed in tubuloacinar SG cells, which emphasizes the role of these cells in the pathogenesis of SS.

Topics: Adult; Case-Control Studies; Cells, Cultured; Female; Humans; Interleukin-8; Male; Middle Aged; Piperazines; Pyrimidines; Receptors, G-Protein-Coupled; Receptors, Histamine; Receptors, Histamine H4; RNA, Messenger; Salivary Glands; Sialadenitis; Sjogren's Syndrome; Vascular Endothelial Growth Factor A

The present study aimed to investigate the salivary chemokine levels in patients with primary SS (pSS) and compare them with those in patients with non-SS sicca symptoms or non-sicca controls.. Unstimulated and stimulated whole saliva samples were obtained from pSS patients (n = 30) and age- and gender-matched patients with non-SS sicca (n = 30) and non-sicca healthy controls (n = 25). Salivary CCL2, CCL3, CCL4, CXCL8 and CXCL10 levels were measured using a Luminex bead-based multiplex assay.. Patients with pSS had significantly different distributions of salivary CCL3 (P = 0.0001 by the Kruskal-Wallis test), CCL4 (P < 0.00001), CXLC8 (P < 0.0001) and CXCL10 (P < 0.05) levels in unstimulated saliva and all chemokine levels in stimulated saliva when compared with non-SS sicca and non-sicca controls. In comparison with chemokine production rate, the CXCL8 and CXCL10 production rates were significantly higher in pSS than in non-SS sicca controls (P < 0.01 by the Mann-Whitney test). Logistic regression analyses revealed that salivary CXCL8 (P < 0.05) and CXCL10 (P < 0.05) were the significant discriminating chemokines between the pSS and non-SS sicca groups. Although CXCL8 and CXCL10 levels were not correlated with the focus scores, CXCL8 and CXCL10 levels were significantly associated with salivary gland dysfunction.. These results support the notion that CXCL8 or CXCL10 chemokine plays a role in the pathogenesis of pSS.

Topics: Adult; Aged; Case-Control Studies; Chemokine CXCL10; Chemokines; Female; Humans; Interleukin-8; Male; Middle Aged; Predictive Value of Tests; Saliva; Salivary Glands; Sjogren's Syndrome

Prolonged inflammation can be detrimental because it may cause host toxicity and tissue damage. Indeed, excessive production of inflammatory cytokines is often associated with many autoimmune diseases. In this study we demonstrate that the anti-Ro/SSA autoantibodies (Abs) stimulate the production of pro-inflammatory cytokines IL-6 and IL-8 by human healthy salivary gland epithelial cells (healthy SGEC). The secretion of these cytokines is due to amphiregulin (AREG) that is overexpressed in healthy SGEC treated with anti-Ro/SSA Abs and in Sjögren's syndrome. We have discovered that the up-regulation of AREG occurs through TNF-alpha produced following anti-Ro/SSA Abs treatment. The gene silencing technique was used to study the AREG-TNF-alpha-IL-6/IL-8 secretion pathway, demonstrating that: (i) TNF-alpha gene silencing provokes a significant decrease of proinflammatory cytokines production and AREG expression in anti-Ro/SSA Abs-treated healthy SGEC; (ii) AREG gene silencing has a potent inhibitory effect on TNF-alpha-induced IL-6 and IL-8 secretion in healthy SGEC treated with anti-Ro/SSA Abs. These findings indicate that TACE-mediated AREG shedding plays a critical role in TNF-alpha-induced IL-6 and IL-8 secretion by the human healthy salivary gland epithelial cells, suggesting that this may be one of the possible intracellular mechanisms involved in the salivary glands inflammatory response in Sjögren's syndrome.

Topics: ADAM Proteins; ADAM17 Protein; Amphiregulin; Autoantibodies; Cells, Cultured; EGF Family of Proteins; Enzyme Activation; Epithelial Cells; Furin; Gene Expression Regulation; Glycoproteins; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-6; Interleukin-8; Ribonucleoproteins; RNA, Small Interfering; Salivary Glands; Signal Transduction; Sjogren's Syndrome; Tumor Necrosis Factor-alpha

To evaluate the role of pro-inflammatory cytokines interleukin-8 (IL-8) and interferon-gamma (IFN-gamma) in pathogenesis of Sjogren's syndrome of dry eye (SS--dry eye), and in induction of ocular changes in this disease.. Tear samples were collected from 25 patients with Sjogren's syndrome of dry eye and 33 healthy volunteers. Cytokine levels were determined by ELISA. Ophthalmic examinations, including tests for dry eye, were used to study the ocular surface. The levels of these cytokines in tears and dry eye findings were compared.. The tears level of IL-8 and IFN-gamma in SS--dry eye patients were significantly higher than those in controls. We found positive correlation between the tears levels of pro-inflammatory cytokines and dry eye findings (subjective and objective assessments and diagnostic tests).. The elevated level of pro-inflammatory cytokines in tears fluid of patients with Sjogren's syndrome of dry eye may be important factor in the pathogenesis of this disease. Significant correlation between tears level of cytokines and dry eye findings suggest, that these cytokines induce inflammatory changes of ocular surface in Sjogren's syndrome of dry eye.

Topics: Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interferon-gamma; Interleukin-8; Male; Ophthalmoscopy; Sjogren's Syndrome; Tears

Our previous gene expression analysis suggested that conjunctival epithelial cells of Sjögren's syndrome (SS) are inclined to hyper-proliferation and keratinisation status. The goal of this study is to elucidate whether such pathological situations really exist in the conjunctival epithelium of SS. Also, involvement of inflammatory cytokines in this disease was investigated. Conjunctival tissues or cells obtained from 12 SS patients and 13 normal subjects were subjected to indirect immunostaining to analyse expression of transglutaminase 1 (TGase1), involucrin, keratins 1, 4, 10 and 13. The number of proliferative cells was also analysed by immunostaining of Ki67 antigen. Additionally, changes in gene expression of TGase1 and involucrin after stimulation by IL-1 or IFN-gamma were quantified by real-time RT-PCR. TGase1 and involucrin were up-regulated in the conjunctival epithelium of SS patients. Although not statistically significant, Ki67 positive proliferative cells were slightly increased in SS patients. IFN-gamma stimulation significantly up-regulated TGase1 and unexpectedly repressed involucrin gene expression. IL-1 did not render any significant changes in the expression of these genes. These results suggest the existence of pathological keratinisation in the conjunctival epithelium of SS and also support our hypothesis that inflammatory cytokines may be involved in the ocular surface pathological changes in SS.

Topics: Aged; Biomarkers; Case-Control Studies; Cell Proliferation; Cells, Cultured; Conjunctiva; Epithelium; Female; Fluorescent Antibody Technique, Indirect; Gene Expression; HLA-DR Antigens; Humans; Interferon-gamma; Interleukin-1; Interleukin-8; Keratins; Middle Aged; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; Sjogren's Syndrome; Statistics, Nonparametric; Transglutaminases; Up-Regulation

The present study aimed to compare the cellular pattern and structural changes in the airways of patients with primary Sjögren's syndrome (pSS) with healthy controls. Bronchial biopsy specimens were obtained from seven subjects with pSS and seven healthy controls. All the patients with pSS had increased bronchial responsiveness to methacholine. In the biopsies inflammatory cells, cytokine-producing cells, tenascin and laminin were visual zed by immunostaining. Patients with pSS had a higher number of neutrophils and mast cells than healthy controls, while the number of eosinophils was similar in the two groups. The number of IL-8-positive cells was higher in pSS butthe numbers of IL-4-and IL-5-positive cells were not significantly different between pSS and healthy controls. The numbers of T cells in patients with pSS were higher than in healthy controls, while the numbers of CD25-positive cells were similar to the healthy controls. The degree of epithelial integrity in patients with pSS was significantly lower than in the control group and the tenascin and laminin layers were significantly thicker in the pSS group. There was a correlation between the number of mast cells and the thickness of the tenascin and laminin layers in pSS. In conclusion, we found that the cellular pattern in the bronchial mucosa of patients with pSS displayed large numbers of neutrophils, mast cells and T-lymphocytes. These changes in inflammatory cell numbers seemed to relate to the observed increased epithelial damage and structural changes of the subepithelium. The structural findings, but not the pattern of inflammatory cells, are shared with atopic asthma and may relate to the increased bronchial hyper-responsiveness seen in both diseases.

Topics: Adult; Biopsy; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Case-Control Studies; Eosinophils; Female; Humans; Interleukin-4; Interleukin-5; Interleukin-8; Laminin; Male; Mast Cells; Methacholine Chloride; Middle Aged; Neutrophils; Sjogren's Syndrome; Statistics, Nonparametric; T-Lymphocytes; Tenascin

To investigate the expression and source of chemokines in minor salivary gland biopsies (MSGs) in patients with Sjögren's syndrome (SS).. Immunohistochemical analysis was used to determine the pattern of chemokine expression in MSGs from patients with (n=6) and without (n=5) SS, as well as to examine the phenotype of both resident and infiltrating cells expressing chemokines.. Significant differences in the number of infiltrating mononuclear (MN) cells in patients with and without SS were noted. Ductal epithelial cells of SS biopsies expressed significantly increased levels of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, interleukin-8 (IL-8) and RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted). Biopsies from patients with SS showed that MIP-1beta was expressed by 51% of infiltrating cells, while 41% expressed MIP-1alpha, whereas 22 and 7% expressed RANTES and IL-8, respectively.. Chemokines expressed by ductal epithelial cells may attract circulating leucocytes, in particular CD4+ T cells, towards the site of inflammation, thereby orchestrating the influx of MN cells characteristically seen in MSGs in SS. Chemokines may be induced directly by a putative triggering agent for SS, or secondary to the release of pro-inflammatory cytokines produced by epithelial cells. These findings further implicate epithelial cells as playing a major role in the pathogenesis of SS and implicate chemokines in the leucocyte recruitment in this setting.

Topics: Cell Count; Cell Movement; Chemokine CCL3; Chemokine CCL4; Chemokine CCL5; Chemokines; Epithelial Cells; Female; Humans; Immunoenzyme Techniques; Interleukin-8; Leukocytes, Mononuclear; Macrophage Inflammatory Proteins; Salivary Glands, Minor; Sjogren's Syndrome