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IL-13レセプターのサブユニット構造とシグナル伝達機構の検討：村田　興¹, Raj K. Puri², 毛利　博¹ (¹横浜市大・一内、²FDA・CBER)

Subunit structure and Signal transduction mechanism of Interleukin 13 receptor in human skin fibroblasts: (Takashi Murata¹, Raj K. Puri², Hiroshi MOHRI¹ (¹1st Dept. of Internal Med., Yokohama City University, ²Center for Biologics Evaluation and Research, FDA)

IL-13 have been shown to mediate similar effects in human fibroblast cell lines. However, mechanism of IL-13 induced signal transduction is not known. To investigate whether non-transformed normal skin fibroblast cells utilize JAK-STAT signalling pathways as reported for immune and cancer cell lines, we investigated IL-13 receptor structure and signaling mechanisms in these cell lines . We demonstrate here that high affinity IL-13R was expressed in normal skin fibroblast cell lines. Upon ¹²⁵I-IL-13 crosslinking a 〜70 kDa band was observed in sk559 and sk574 cell lines. On the other hand, in RT-PCR mRNA of IL-13Rα, IL 13Rα' and IL-4Rβchains were expressed, however IL-2Rγ chain was not expressed in all cell lines examined. We also analyzed the signal transduction mechanism of IL-13R of these cell lines. The JAK2 and Tyk2 were phosphorylated in response to IL-4 or IL-13 in sk559 and sk574 cell lines. STAT6 was also activated in response to both interleukins. IRS-1 was constitutively phosphorylated and its phosphorylation level was augmented in response to both IL-13 or IL-4. These results suggest that signal transduction through IL-13 and IL-4 receptors in normal non-transformed human fibroblast cell lines is similar which may be responsible for redundant effects of these two cytokines. In addition, JAK2 tyrosine kinase appear to play a major role in signal transduction instead of JAK3 kinase.