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- Min-Jung Kim
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
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- Joo-Yeon Yoo
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
説明
<jats:title>Abstract</jats:title> <jats:p>Caspase-1 is an inflammatory caspase that controls the activation and secretion of the inflammatory cytokines, IL-1β and IL-18. We observed that cellular levels of retinoic acid-inducible gene-I (RIG-I) were enhanced when the pan-caspase inhibitor Z-VAD-fmk or caspase-1-specific inhibitor Z-WEHD-fmk blocked caspase activity. Overexpression of caspase-1 reduced cellular levels of RIG-I and inhibited RIG-I-mediated signaling activity. Enzymatic activity of caspase-1 was necessary to control RIG-I, although it was not a substrate of proteolytic cleavage by caspase-1. Caspase-1 physically interacted with full length RIG-I, but not with mutant forms lacking either the amino- or carboxyl-terminal domains. RIG-I was present in the supernatant of cells transfected with active caspase-1 but not with caspase-4. Stimulating cells with LPS and ATP also induced secretion of endogenous RIG-I in macrophages. Our data suggest a novel mechanism that negatively regulates RIG-I-mediated signaling activity via caspase-1-dependent secretion of RIG-I protein.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 181 (10), 7324-7331, 2008-11-15
Oxford University Press (OUP)