title: Kurarinone regulates immune responses through regulation of the JAK/STAT and TCR-mediated signaling pathways.
abstract: Sophora flavescens is a medicinal herb that contains flavonoids and quinolizidine alkaloids and has a wide range of biological activities due to its anti-inflammatory, anti-bacterial and anti-cancer properties. We isolated a series of flavonoids from the roots of Sophora flavescens and examined their ability to inhibit immune responses. Among the flavonoids, kurarinone exhibited the strongest inhibitory effect on immune responses. Kurarinone suppressed the differentiation of CD4(+) T cells by inhibiting the expression and production of T-cell lineage-specific master regulators and cytokines. Our results also demonstrated that kurarinone directly suppressed the cytokine-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling and T-cell receptor (TCR) pathways. In two established animal models of chronic inflammatory skin disease, one in which psoriasis-like skin disease was induced by an interleukin 23 (IL-23) injection into mouse ears and another in which 2,4,6-trinitrochlorobenzene (TNCB) application on the abdomens of mice was used to induce contact dermatitis, kurarinone repressed disease development by inhibiting the expression of pro-inflammatory mediators, including cytokines, chemokines and enzyme in murine ear skin. This study provides new evidence that kurarinone may ameliorate chronic inflammatory skin diseases through the suppression of pathogenic CD4(+) T-cell differentiation and the overall immune response.
authors: Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul 137-040, Republic of Korea.
authors: Byung-Hak
authors: BH
authors: Kim
authors: Kwang-Min
authors: KM
authors: Na
authors: Ikhoon
authors: I
authors: Oh
authors: Inn-Hye
authors: IH
authors: Song
authors: Yun Sang
authors: YS
authors: Lee
authors: Jongheon
authors: J
authors: Shin
authors: Tae-Yoon
authors: TY
authors: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D053612:Janus Kinases / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D050791:STAT Transcription Factors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D005419:Flavonoids; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell; D050791:STAT Transcription Factors; C411319:kurarinone; D053612:Janus Kinases