Abstract
HSP27 is a member of the small HSP family which has been linked to different signaling pathways regulating critical cellular functions. But the role of HSP27 in LPS-induced inflammatory signaling pathways is still unclear. In the present study, both overexpression and RNA interference experiments indicated that HSP27 increased LPS-induced expression of iNOS and COX-2 and release of NO/PGE2 through enhancing NF-kappaB but not MAPK activation. The effects of HSP27 on LPS-induced iNOS/COX-2 expression and relative signaling cascade were closely related with the phosphorylation of HSP27. Further studies have shown that HSP27-regulated LPS-induced activation of NF-kappaB by interacting with TRAF6 and increasing the association of TRAF6-IKKgamma. This could be a probable mechanism by which HSP27 modulates LPS-induce inflammatory signaling pathways. Thus, HSP27 may play a potential role in regulating inflammatory responses in immunologic system.
Copyright 2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Cloning, Molecular
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / metabolism*
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Dinoprostone / metabolism
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HSP27 Heat-Shock Proteins / genetics
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HSP27 Heat-Shock Proteins / immunology
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HSP27 Heat-Shock Proteins / metabolism*
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Humans
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I-kappa B Kinase / metabolism
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Inflammation
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Lipopolysaccharides / immunology
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Lipopolysaccharides / metabolism*
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Macrophages / immunology
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Macrophages / metabolism*
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Macrophages / pathology
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / metabolism*
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RNA, Small Interfering / genetics
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Signal Transduction / genetics
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Signal Transduction / immunology
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TNF Receptor-Associated Factor 6 / metabolism
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Transcriptional Activation / genetics
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Transcriptional Activation / immunology
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Transgenes / genetics
Substances
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HSP27 Heat-Shock Proteins
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Lipopolysaccharides
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NF-kappa B
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RNA, Small Interfering
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TNF Receptor-Associated Factor 6
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Nitric Oxide
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2
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PTGS2 protein, human
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I-kappa B Kinase
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Dinoprostone