Function Of SIL-6R/Stat3 Signaling In The Pathological Progress Of Psoriasis And The Possibility And Validity Of Berberine In Treatment Of Psoriasis

Part1:Function of sIL-6R/Stat3 signaling in the pathological progress of psoriasis.Psoriasis is a common,chronic inflammatory skin disease that is characterized by perproliferation of epidermis and aberrant differentiation of keratinocytes.Stat3,a known transcription factor that induces inflammation and regulate cell differentiation,plays a crucial role for the pathogenesis development of psoriasis.IL-6 is a pleiotropic pro-inflammatory cytokine with a wide range of biological activities in immune system,beside influencing the biological function of keratinocytes,recent studies have demonstrated that IL-6 has a very variety of role in regulation of T cell differentiation,especially for balancing the inflammatory Th17 cells and regulatory T(Treg)cells.IL-6 induced Stat3 activation rely on two types of receptors,including IL-6-—? submit(IL-6R)and p submit(GP130),there are two forms of IL-6R existed,including the membrane-binding forms receptor(mIL-6R)and the soluble forms receptor(sIL-6R).Although the mGP130 expressed in all types of cells,the mIL-6R were specifically expressed in hepatocytes and some kinds of immunocytes.The sIL-6R was normally generated from the shedding of mIL-6R by ADAM 17,therefore,the up-regulated expression of serum sIL-6R plays a key role for the activation of Stat3 signaling pathway.In this paper,we first demonstrated that the serum level of sIL-6R was up-regulated in psoriatic patients,in compared with the normal healthy individual,there are mild increase of mIL-6R expression was found in the tissue slices of the lesional skin.Secondly,we found that the variations of two SNPs of IL-6R gene are associated with the serum level of sIL-6R in Psoriasis.More over,the results of flow cytometry experiment showed that the expression of mIL-6R are up-regulated in total PBMC and T cell,which in compared with its slightly down-regulated expression in Th cells.In addition,results from both in vivo and in vitro studies all indicated that IL-6/stat3 signaling could be over-activated by the existence of extra amount of sIL-6R,these results suggested that IL-6R could stimulate the abnormal cell differentiation of keratinocytes.Part2:Berberine inhibit proliferation of HaCaT cells and reverse psoriatic lesion in IMQ induced psoriasis model via Stat3 signaling.Psoriasis is a common,chronic inflammatory skin disease that is characterized by the over proliferation of epidermis and aberrant differentiation of keratinocytes.Although the pathological machnism of this disease is not completely understand,it has been well established that psoriasis is considered to be a T cell mediated autoimmune disease,the increased activaiton of CD4+ T cells and especially the abnormal differentiation of Thl7 cells seems to play a crucial role during this process.Recently,the wellknown common treatments of Psoriasis including immunosuppressive agents,topical agents,systemic therapies and UVB phototherapy.However,the high therapeutic cost expense and the frequence of relapse after withdrawal of treatment forced us to look for more safer,high efficiency and economic drugs for the targeting treatment of psoriasis.Berberine,a benzylisoquinoline alkaloid,existed as an active compound in numerous medicinal plants and has diverse pharmacological properties.It has been used widely in traditional Chinese medicine for its antimicrobial,antiprotozoal,antidiarrheal and antitrachoma activity.In recent years,there are several clinical and preclinical studies demonstrated that the ameliorative effect of berberine against several disorders including neurological,metabolic and cardiological problems.In this paper,we first demonstrated that in response to the Th17 related cytokines IL-6/IL-22 stimulis,the activation of Stat3 and the expressions of its down-stream proteins was all significantly inhibited by berberine.In addition,in IMQ-induced psoriasis mice model,both oral and topical administration of berberine could significantly alleviate the pathological phenotype of the skin demage.Taken together,study provides evidence that Berberine might be a new,safe,high efficiency and economic drug for the targeting treatment of psoriasis.