Kurarinone regulates immune responses through regulation of the JAK/STAT and TCR-mediated signaling pathways

• Published in: Biochemical pharmacology Vol. 85; no. 8; pp. 1134 - 1144
• Main Authors: Kim, Byung-Hak, Na, Kwang-Min, Oh, Ikhoon, Song, Inn-Hye, Lee, Yun Sang, Shin, Jongheon, Kim, Tae-Yoon
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 15.04.2013
• Subjects: animal models; Animals; anticarcinogenic activity; Antioxidants - pharmacology; Autoimmune disease; CD4+ T cell; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Cell Differentiation - drug effects; chemokines; contact dermatitis; Cytokines - biosynthesis; ears; flavonoids; Flavonoids - pharmacology; Humans; Immune response; Immunosuppressive Agents - pharmacology; interleukins; JAK/STAT; Janus Kinases - physiology; Kurarinone; medicinal plants; Mice; Mice, Inbred C57BL; non-specific protein-tyrosine kinase; quinolizidine alkaloids; Receptors, Antigen, T-Cell - physiology; roots; signal transduction; Signal Transduction - drug effects; Sophora; Sophora flavescens; STAT Transcription Factors - physiology; T-cell receptor; T-lymphocytes; transcription factors; T-cell receptor; Kurarinone; Autoimmune disease; CD4+ T cell; Immune response; JAK/STAT
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2013.01.005

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.