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RIP 2/ RICK ‐Dependent Cytokine Production Upon Yersinia enterocolitica Infection in Macrophages with TLR 4 Deficiency
Author(s) -
Jeong Y.J.,
Kim C.H.,
Kim J.C.,
Oh S.M.,
Lee K.B.,
Park J.H.,
Kim D.J.
Publication year - 2013
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12100
Subject(s) - yersinia enterocolitica , proinflammatory cytokine , cytokine , lipopolysaccharide , biology , innate immune system , immune system , microbiology and biotechnology , yersinia , immunology , macrophage , inflammation , bacteria , biochemistry , genetics , in vitro
Receptor‐interacting protein 2 ( RIP 2) is a caspase recruitment domain ( CARD )‐containing serine/threonine kinase that is activated by NOD 1 or NOD 2 recognition of their ligands and essential for the activation of NF ‐κB and mitogen‐activated protein kinase ( MAPK ). RIP 2 has been known to play an important role in innate immune responses against certain bacterial infection. However, the role and interplay of RIP 2 with TLR signalling on cytokine production in macrophages against Yersinia enterocolitica infection remains poorly understood. In the present study, we examined whether RIP 2 is essential for Yersinia‐induced production of cytokines in macrophages. Our results showed that naïve RIP 2‐deficient macrophages produced similar level of IL ‐6, TNF ‐α and IL ‐10 upon Y. enterocolitica infection compared with wild‐type macrophages. However, the production of IL ‐6, TNF ‐α and IL ‐10 by Y. enterocolitica was impaired in RIP 2‐deficient macrophages after lipopolysaccharide ( LPS ) pretreatment, a TLR 4‐tolerant condition. In addition, RIP 2 inhibitors, SB 203580, PP 2, and gefitinib, reduced IL ‐6 production in TLR 4‐deficient macrophages in response to Y. enterocolitica , whereas they did not affect the cytokines production in WT cells. These results demonstrate that RIP 2 may play an important role in proinflammatory cytokine production in macrophages at the absence of TLR signalling.