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Icroenvironment by senescent becs expressing sasps such as chemokines and cytokines in pbc. Senescent becs may participate in modulation of the inflammatory microenvironment by recruiting monocytes and possibly other types of inflammatory cells, induction of senescence in surrounding cells, and progression of fibrosis via sasp. Very little is known about the mechanism which initiates and maintains sasps, including chemokines [79, 89–91]. Since several types of cellular stress, such as oxidative stress, dna damage by etoposide, and serum deprivation, induced sasps in senescent becs in the present study, and it is plausible that these stresses may induce sasps via a common mechanism in the senescent state. Similarly, sasps in senescent becs in pbc may contribute to the activation of the innate immune system around the injured bile ducts. Upregulation of several cytokines and chemokines has been reported in damaged bile ducts in pbc [39, 47, 56]. This study raised the possibility that most of such cytokine and chemokine profiles may be included in sasps. Senescence is both regulated by and regulates the extracellular environment. 7. Summary pbc, like most polygenic autoimmune diseases, clearly belongs to the “complex disease” category that is attributable to the combined effects of multiple environmental and behavioral influences, genetic elements, and perhaps chance. Mitochondrial autoantigens and b-cell and t-cell autoepitopes have been well characterized in pbc; however, the etiology and the relation between amas and bile duct lesions remain to be determined. We emphasized the features of becs in bile duct lesions in pbc, in particular, the unique feature of apoptotic becs which retain immunologically intact pdc-e2 and two novel cellular processes: autophagy and cellular senescence. Autophagy may be a promising cellular mechanism involved in the autoimmune mechanism together with apoptosis. Cellular senescence may be related to the immunopathology of becs by the expression of sasps in pbc. http://cheapviagraonlinebestprice.accountant http://viagraonlineforsalecanada.accountant http://buycheapgenericviagrapillsonline.accountant buyviagraonlinedifferentdosage.accountant buygenericviagraonlinewithoutprescription.accountant genericviagraonlinecheappharmacy.accountant Further studies are warranted to completely disclose the pathogenesis of pbc. Acknowledgment this study was supported in part by a grant-in aid for scientific research (c) from the ministry of education, culture, sports and science and technology of japan (18590325 and 2590366). References m. E. Gershwin, i. R. Mackay, a. Sturgess, and r. L. Coppel, “identification and specificity of a cdna encodin. Ballybrack, Moville, Co. Donegal

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