title: RIP2/RICK-dependent cytokine production upon Yersinia enterocolitica infection in macrophages with TLR4 deficiency.
abstract: Receptor-interacting protein 2 (RIP2) is a caspase recruitment domain (CARD)-containing serine/threonine kinase that is activated by NOD1 or NOD2 recognition of their ligands and essential for the activation of NF-κB and mitogen-activated protein kinase (MAPK). RIP2 has been known to play an important role in innate immune responses against certain bacterial infection. However, the role and interplay of RIP2 with TLR signalling on cytokine production in macrophages against Yersinia enterocolitica infection remains poorly understood. In the present study, we examined whether RIP2 is essential for Yersinia-induced production of cytokines in macrophages. Our results showed that naïve RIP2-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 RIP2-deficient macrophages after lipopolysaccharide (LPS) pretreatment, a TLR4-tolerant condition. In addition, RIP2 inhibitors, SB203580, PP2, and gefitinib, reduced IL-6 production in TLR4-deficient macrophages in response to Y. enterocolitica, whereas they did not affect the cytokines production in WT cells. These results demonstrate that RIP2 may play an important role in proinflammatory cytokine production in macrophages at the absence of TLR signalling.
authors: Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Republic of Korea.
authors: Y-J
authors: YJ
authors: Jeong
authors: C-H
authors: CH
authors: Kim
authors: J-C
authors: JC
authors: Kim
authors: S-M
authors: SM
authors: Oh
authors: K-B
authors: KB
authors: Lee
authors: J-H
authors: JH
authors: Park
authors: D-J
authors: DJ
authors: Kim
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000077156:Gefitinib; D007093:Imidazoles / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000172:deficiency* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015009:Yersinia Infections / Q000276:immunology*; D015008:Yersinia enterocolitica
chemical_list: C412373:AG 1879; D004791:Enzyme Inhibitors; D007093:Imidazoles; D015850:Interleukin-6; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D011799:Quinazolines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse; C093642:SB 203580; D000077156:Gefitinib