Regulation of lipopolysaccharide-induced inflammatory response by heat shock protein 27 in THP-1 cells.

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.