TLR5 involvement in attenuated IL-8 production in nuclear decorin silenced oral mucosal dysplastic keratinocytes and squamous cell carcinoma

作     者：Nyla Dil Abhijit G. Banerjee 

作者机构：Department of Oral Biology Faculty of Dentistry University of Manitoba Winnipeg Canada Center for Genomic Bio-Medicine and Research Institute Durg Chhattisgarh India Department of Oral Biology Faculty of Dentistry University of Manitoba Winnipeg Canada Department of Immunology and Department of Medical Microbiology and Infectious Diseases Faculty of Medicine University of Manitoba Winnipeg Canada 

出 版 物：《American Journal of Molecular Biology》 (美国分子生物学期刊（英文）)

年 卷 期：2013年第3卷第4期

页      面：248-254页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Oral Cancer Proteoglycans Flagellin DAMP Mucosal Cancer TLR5 PAMP IL-8 SLRP Nuclear decorin 

摘      要：Head and neck cancer is one of the most prevalent cancers in the world. Roughly half of these malignancies originate from oral mucosa and constitute Oral squamous cell carcinomas. Despite many advances in diagnostic and therapeutic regimens, five year survival rate remains at roughly 50 %, indicating the need for in depth understanding of the oral squamous cell carcinoma immunobiology. We have previously shown that in human dysplastic oral keratinocytes (DOK) and malignant squamous cells carcinoma (SCC-25), multifunctional proteoglycan decorin is aberrantly expressed and localized in the nucleus bound to nuclear EGFR. In vitro nuclear decorin knockdown significantly reduced IL-8 and IL8-dependent migration, invasion and angiogenesis in these cells. Since toll-like receptor (TLR) signalling leads to IL-8 production we examined here if these receptors play a role in decorin silencing mediated reduction in IL-8 levels. We have used immunological and molecular techniques to study toll-like receptors involvement in attenuated IL-8 production in nuclear decorin silenced (stable knockdown) oral mucosal dysplastic keratinocytes and squamous carcinoma cells. We show that nuclear decorin silenced DOK and SCC-25 cells show marked diminution of TLR5 mRNA and protein expression compared with respective controls that translated into loss of function in response to appropriate TLR ligand. In these mucosal oral epithelia, decorin stable knockdown significantly down-regulated IL-8 production following activation with TLR5 ligand flagellin. These data suggest that decorin silencing interferes with IL-8 production, in part, by altering TLR5 expression and signaling in dysplastic and malignant oral epithelia. This study highlights the significance of TLR5 expression and signaling in mucosal cancers.