@article{oai:u-ryukyu.repo.nii.ac.jp:02017765, author = {Lin, Yanhui and Kato, Seiya}, issue = {3・4}, journal = {琉球医学会誌 = Ryukyu Medical Journal}, note = {Introduction: Macrophages are involved in various inflammatory processes. Although the therapeutic potential of interleukin-4 (IL-4)-mediated immunomodulation has been proposed, it has not yet been established. The type I IL-4 receptor (IL-4RI) consists of IL-4R α and a common γ chain, whereas the type II IL-4R (IL-4RII) is a heterodimer of IL-4R a and IL-13R α 1. In the present study, we assessed the selective activation of IL-4R isoforms in the mouse macrophage cell lines, Mm1 and J774.1, to investigate the role of receptor-specific signaling in inflammatory activation. Materials and Methods: The plasmid expressing murine IL-4/ Q116E, which is analogous to the human IL-4RI-specific agonist IL-4/ R121E, was transfected to assess IL-4RI activation. IL-4RII activation was induced by IL-13. Activation of IL-4R isoforms was confirmed by the activation of signal transducer and activator of transcription 6 (STAT6). Lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) induction was examined using real-time polymerase chain reaction. LPS plus interferon- γ (INF- γ )-stimulated inducible nitric oxide synthase induction was tested using western blotting. Results: IL-4/ Q116E induced STAT6 activation in Mm1 cells but not in J774.1 cells. In Mm1 cells, IL-4/ Q116E-induced STAT6 activation was inhibited by kaempferol, a specific inhibitor for Janus kinase 3 (JAK3). IL-4/Q116E did not exhibit anti-inflammatory activity in either macrophage cell line. However, IL-13 inhibited inflammatory activation of these cells. Conclusions: Our data suggest that Mm1 cells expressed both IL-4RI and IL-4RII, whereas J774.1 cells expressed only IL-4RII. Although IL-4R isoform expression pattern was diverse in these two macrophages, the IL-4-mediated antiinflammatory effect was thought to be largely dependent on IL-4RII-mediated signaling. Thus, we could further conclude that IL-4 signaling plays a pivotal role in the regulation of macrophage inflammatory proprieties. Understanding IL-4-mediated anti-inflammatory signaling in macrophages may be beneficial for the development of therapeutics., 論文}, pages = {69--78}, title = {[原著]Type II interleukin-4 receptor-mediated anti-inflammatory response in Mm1 and J774.1 macrophages}, volume = {32} }