title: Regulation of Salmonella flagellin-induced interleukin-8 in intestinal epithelial cells by muramyl dipeptide.
abstract: Toll-like receptor 5 (TLR5) and nucleotide-binding oligomerization domain 2 (Nod2) are two important pattern recognition receptors involved in innate immunity to invading pathogens. Flagellin, recognized by TLR5, is Salmonella's dominant pro-inflammatory determinant in intestinal epithelial cells (IECs). Nod2 has played a pivotal role in protecting against intestinal bacterial infection. Therefore the aim of the study is to investigate regulation of Salmonella flagellin-induced interleukin (IL)-8 (IL-8) in IECs by Nod2 agonist, muramyl dipeptide (MDP). We found that MDP by itself induced only a weak IL-8 secretion in Caco-2 cells. However, it did show synergistic enhancement on flagellin-induced IL-8 production in Caco-2 cells, possibly caused by flagellin-mediated enhanced Nod2 recruitment into cell membrane. By Western blot and siRNA, we showed ERK and NF-κB, Nod2 and Rip2 were involved in the synergistic effect of MDP. These findings suggested that the cooperation of TLR5 and Nod2 in IECs regulates inflammatory response to Salmonella infection.
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. huang817@adm.cgmh.org.tw
authors.forename: Fu-Chen
authors.initials: FC
authors.lastname: Huang
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D018938:Caco-2 Cells; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005408:Flagellin / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012486:Salmonella typhimurium / Q000737:chemistry* / Q000276:immunology; D015398:Signal Transduction; D051198:Toll-Like Receptor 5 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D005408:Flagellin; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D048049:Extracellular Signal-Regulated MAP Kinases