A potential role of the GRO-alpha/CXCR2 system in Sjogren%26apos;s syndrome: regulatory effects of pro-inflammatory cytokines

作者：Lisi Sabrina^*; Sisto Margherita; Lofrumento Dario Domenico; D' Amore Massimo; De Lucro Raffaella; Ribatti Domenico

来源：Histochemistry and Cell Biology, 2013, 139(2): 371-379.

DOI：10.1007/s00418-012-1035-z

• GRO-alpha
• CXCR2
• Sjogren%26apos
• s syndrome
• Salivary gland

Chemokines, small pro-inflammatory cytokines, are involved in migration of inflammatory cells in inflamed tissues and recent studies established their role in angiogenesis, hematopoiesis, cancer and autoimmune conditions. Growth related oncogene-alpha (GRO-alpha), a member of the CXC chemokine family, and its receptor CXCR2 are involved in the inflammatory processes. Since there is no previous report that supports a possible role of GRO-alpha/CXCR2 receptor complex during inflammation and neovascularization existing in the autoimmune disease Sjogren%26apos;s syndrome (SS), in this study, we examined CXCR2 and its ligand GRO-alpha expression in SS tissues. Immunohistochemistry revealed that GRO-alpha and its receptor CXCR2 were expressed at high levels in diseased tissues compared to healthy controls. In addition, human salivary gland epithelial cells (SGEC) cultures were submitted to a pro-inflammatory microenvironment using cytokines IL-6 and TNF-alpha in order to demonstrate that CXCR2 may change its initial expression pattern to another under inflammatory condition. The data show an increased expression of CXCR2 depending on the inflammatory cytokine used in culture in a time-dependent manner. Furthermore, silencing of the pro-angiogenic chemokine GRO-alpha is proportionally correlated with decreased expression of CXCR2 in pro-inflammatory cytokine-stimulated SGEC indicating the GRO-alpha/CXCR2 complex as a novel therapeutic target for the chronic inflammatory disease Sjogren%26apos;s syndrome.

• 出版日期2013-2