题名：Monarch-1 suppresses non-canonical NF-kappaB activation and p52-dependent chemokine expression in monocytes.
作者：Lich JD, Williams KL, Moore CB, Arthur JC, Davis BK, Taxman DJ, Ting JP
来源：J Immunol[IF=6.387]. 2007 Feb 1 178(3):1256-60
摘要： John D. Lich, Kristi L. Williams, Chris B. Moore, Janelle C. Arthur, Beckley K. Davis, Debra J. Taxman and Jenny P-Y. Ting2
Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, NC 27599
CATERPILLER (NOD, NBD-LRR) proteins are rapidly emerging as important mediators of innate and adaptive immunity. Among these, Monarch-1 operates as a novel attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. However, the molecular mechanisms by which Monarch-1 performs this important function are not well understood. In this report, we show that Monarch-1 inhibits CD40-mediated activation of NF-B via the non-canonical pathway in human monocytes. This inhibition stems from the ability of Monarch-1 to associate with and induce proteasome-mediated degradation of NF-B inducing kinase. Congruently, silencing Monarch-1 with shRNA enhances the expression of p52-dependent chemokines.
This article is selected and evaluated by Faculty of 1000 Biology, F1000 Factor 3.0
E. Charles Snow
University of Kentucky Medical Center, United States of America
This interesting paper demonstrates that Monarch-1, a member of the Caterpiller protein family, suppresses monocyte participation during inflammatory responses by directly blocking the non-canonical NF-kappaB pathway required for inflammatory cytokine production. The results clearly show that elevated expression of Monach-1 targets the rapid turnover of NF-kappaB-inducing kinase (NIK), the kinase essential for proper proteolytic processing of p100 to the biologically active p52 peptide. This paper reveals what may turn out to be the key intracellular regulatory mechanism responsible for dampening the release, by activated monocytes, of pro-inflammatory cytokines during innate immune responses.
Competing interests: None declared
Evaluated 15 Feb 2007 1ku 5.
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