Tissue-specific regulation of CXCL9-10-11 chemokines in keratinocytes: Implications for oral inflammatory diseaseReport as inadecuate




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The IFN-γ-inducible chemokines CXCL9, CXCL10, and CXCL11 play a key role in many inflammatory conditions, particularly those mediated by T cells. Therefore, the production of these chemokines in peripheral tissues could be instrumental in the pathophysiology of tissue-specific immunological diseases such as oral lichen planus OLP. In the present study, we assessed the production of keratinocyte-derived CXCL9-10-11 under basal and inflammatory conditions and investigated whether these chemokines were involved in the pathogenesis of OLP. We used semi-quantitative PCR, ELISA, chemotaxis assays, and fluorescence-activated cell sorting FACS to assess the expression and functional role of CXCL9-10-11 in oral keratinocytes three strains of normal human oral keratinocytes NHOK, and the H357 oral cancer cell line in the presence or absence of IFN-γ. CXCL9-10-11 were also assessed in tissues from normal patients and those with oral lichen planus OLP. The time course study in oral keratinocytes treated with IFN-γ showed that expression of CXCL9-10-11 chemokines was significantly enhanced by IFN-γ in a time-dependent manner. In particular, CXCL10, a prominent chemokine that was overexpressed by IFN-γ-stimulated NHOK, was able to effectively recruit CD4 lymphocytes, mainly CD4+CD45RA- cells. Significantly higher levels of CXCL9-10-11 were found in tissues from patients with OLP compared to normal oral mucosa. Taken together, the results demonstrate that normal oral keratinocytes produce chemotactic molecules that mediate T cell recruitment. This study furthers understanding of chemokine production in oral keratinocytes and their role in the pathophysiology of oral mucosa, with particular relevance to OLP.



Author: Alison Marshall, Antonio Celentano , Nicola Cirillo, Michael McCullough, Stephen Porter

Source: http://plos.srce.hr/



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