Zinc suppresses Th17 development via inhibition of STAT3 activation
| Autor: | Masaaki Murakami, Minoru Kanamoto, Chika Kitabayashi, Toru Atsumi, Shintaro Hojyo, Naoko Ueda, Ichiro Azuma, Toshio Hirano, Wakana Ohashi, Hiroshi Hirota, Toshiyuki Fukada |
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| Rok vydání: | 2010 |
| Předmět: |
STAT3 Transcription Factor
Immunology chemistry.chemical_element Zinc Biology Mice Structure-Activity Relationship Immune system Immunology and Allergy Animals Humans STAT3 Transcription factor Cells Cultured chemistry.chemical_classification Cell growth Kinase Interleukin-17 General Medicine Arthritis Experimental In vitro Cell biology Mice Inbred C57BL Enzyme chemistry Biochemistry biology.protein Th17 Cells |
| Zdroj: | International immunology. 22(5) |
| ISSN: | 1460-2377 |
| Popis: | Zinc (Zn) is an essential trace metal required by many enzymes and transcription factors for their activity or the maintenance of their structure. Zn has a variety of effects in the immune responses and inflammation, although it has not been well known how Zn affects these reactions on the molecular basis. We here showed that Zn suppresses T(h)17-mediated autoimmune diseases at lest in part by inhibiting the development of T(h)17 cells via attenuating STAT3 activation. In mice injected with type II collagen to induce arthritis, Zn treatment inhibited T(h)17 cell development. IL-6-mediated activation of STAT3 and in vitro T(h)17 cell development were all suppressed by Zn. Importantly, Zn binding changed the alpha-helical secondary structure of STAT3, disrupting the association of STAT3 with JAK2 kinase and with a phospho-peptide that included a STAT3-binding motif from the IL-6 signal transducer gp130. Thus, we conclude that Zn suppresses STAT3 activation, which is a critical step for T(h)17 development. |
| Databáze: | OpenAIRE |
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