title: Multi-glycoside of Tripterygium wilfordii Hook. f. ameliorates imiquimod-induced skin lesions through a STAT3-dependent mechanism involving the inhibition of Th17-mediated inflammatory responses.
abstract: Multi-glycoside of Tripterygium wilfordii Hook. f.(GTW) possesses anti-inflammatory and immunosuppressive properties, and has been used as a traditional treatment for psoriasis for many years, although the underlying immunological mechanisms remain poorly understood. The T helper (Th)17 cell response is considered to play a major role in the pathogenesis of psoriasis. Th17 cells are implicated in the mechanism of pathogenesis of imiquimod (IMQ)‑induced skin inflammation. Using a mouse model, we demonstrated that GTW protected mice from developing psoriasis-like lesions induced by topical IMQ administration. This protection was associated with significantly decreased mRNA levels of Th17 cytokines such as interleukin (IL)-17A, IL-17F and IL-22 in mouse skin samples as well as fewer IL-17-secreting splenic CD4+ lymphocytes in IMQ-exposed mice. There were no significant effects on the proportion of CD4+ interferon (IFN)-γ+ T cells, CD4+IL-4+ T cells and CD4+CD25+Foxp3+ Treg cells in the spleen cells. Taken together with the unchanged mRNA levels of Th1 cytokine IFN-γ, Th2 cytokine IL-4 and Treg cytokine IL-10 in IMQ-exposed mouse skin following GTW administration, our findings suggest that the immunosuppressive effect of GTW in psoriasis is exerted mainly on Th17 cells, rather than on Th1, Th2 or Treg cells. Furthermore, we showed that GTW suppressed Th17 function through the inhibition of STAT3 phosphorylation. These results have the potential to pave the way for the use of GTW as an agent for the treatment of psoriasis.
authors.affiliation: Department of Pathophysiology, Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, P.R. China.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Di
authors.affiliation: Department of Pathophysiology, Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, P.R. China.
authors.forename: Daiying
authors.initials: D
authors.lastname: Liang
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine, Affiliated with Capital Medical University, Beijing 100010, P.R. China.
authors.forename: Guangzhong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D000634:Aminoquinolines; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology*; D000077271:Imiquimod; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy / Q000379:methods; D020011:Protective Agents / Q000494:pharmacology; D011565:Psoriasis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000378:metabolism; D029757:Tripterygium / Q000737:chemistry*
chemical_list: D000634:Aminoquinolines; D016207:Cytokines; D006027:Glycosides; D018836:Inflammation Mediators; D020381:Interleukin-17; D020011:Protective Agents; D050796:STAT3 Transcription Factor; D000077271:Imiquimod