Chemokine expression and leucocyte infiltration in Sjogren's syndrome

Abstract

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.

Sjögren's syndrome autoantibodies provoke changes in gene expression profiles of inflammatory cytokines triggering a pathway involving TACE/NF-κB

“…31 In addition, to evaluate the specific contribution of IkB-a phosphorylation to TACEinduced NF-kB activation in SGEC, we used the dominant negative super-repressor IkB-a, which disrupts phosphorylation and subsequent degradation, preventing NF-kB nuclear translocation. Following the discovery of proinflammatory cytokines accumulation in functionally and structurally damaged areas of the salivary glands, 3,6 we first assessed any differences in the level of gene expression of inflammatory mediators, such as cytokines/chemokines, in human SGECs treated with the anti-Ro/SSA Abs characterizing SS. The screening for abnormally expressed inflammatory mediators demonstrated that anti-Ro/SSA Abs enhanced the expression of CXC chemokines, CC chemokines, several ILs and their receptors.…”

“…Following the discovery of proinflammatory cytokines accumulation in functionally and structurally damaged areas of the salivary glands, 3,6 and its pathogenic significance in autoimmune diseases, 7,8 we assessed differences in the gene expression levels of inflammatory mediators, such as cytokines/chemokines, in human SGECs treated with the anti-Ro/SSA Abs that characterize SS. In anti-Ro/SSA Abs-treated SGEC we screened for abnormally expressed inflammatory mediators using RT 2 Profiler PCR arrays, a high-throughput technique, designed specifically to target major cytokines and chemokines.…”

“…3,4 Sjögren's syndrome is a systemic chronic inflammatory autoimmune disorder that affects secretory organs such as the salivary and lachrymal glands, 5 and TNF-a production seems to be closely linked to SS. 4,6,7 In addition, proteases such as the TNF-a converting enzyme (TACE) contribute to the autoimmune condition by processing innate inflammatory cytokines and other proteins. 8 Cytokines have a central role in triggering and perpetuating inflammation in the secretory glands, and the imbalance of pro-over anti-inflammatory cytokines results in cumulative damage to the glands impairing the secretory function.…”

Involvement of autoimmunity to REG, a regeneration factor, in patients with primary Sjögren's syndrome

“…We examined the mRNA levels of IL-6 and IL-8, major proinflammatory cytokines produced in MSG in SS patients [27][28][29][30], in MSG specimens. We also examined mRNA levels of IL-6 receptor and gp130 in MSG specimens.…”

Dysregulation of chemokine receptor expression and function by B cells of patients with primary Sjögren's syndrome

“…Chemokines and their corresponding chemokine receptors play an important role in lymphopoiesis, differentiation, homing, recirculation, and immune responses of lymphocyte subsets under physiologic and pathologic conditions (11)(12)(13)(14). The inflamed glands seen in primary SS have been shown to express a unique profile of adhesion molecules, cytokines, and chemokines, including overexpression of CXCL13 (B lymphocyte chemoattractant [BLC]; B cell-attracting chemokine 1 [BCA-1]) mRNA and protein, a central chemokine involved in B cell homing (15)(16)(17), as well as of CCL19, CCL18, CXCL9 (monokine induced by interferon-␥), and CXCL10 mRNA (17,18,19).…”