Nod2 mutation enhances NF-kappa B activity and bacterial killing activity of macrophages.
NOD2, an intracellular sensor of bacteria, are linked to increased susceptibility to bacteria in Crohn's disease (CD). The NOD2 protein is expressed mainly by macrophages and dendritic cells. This study is to examine the role of NOD2 in the innate response of macrophages to bacterial challenge. First, peritoneal macrophages and alveolar macrophages were harvested from WT, Nod2(2939iC), as well as TLR4(-/-) mice and incubated with E. coli or P. aeruginosa. Bacterial killing activity; IL-1beta and TLR4 protein expression; NF-kappaB DNA binding activity assay; as well as IL-1beta, TNFalpha, TLR2, TLR4 and TLR9 mRNA expression of macrophages were examined. We found that alveolar macrophages and peritoneal macrophages of Nod2(2939iC) mice but not WT mice or TLR4(-/-) mice demonstrated a significant increase of E. coli killing activity. Bacterial challenge also induced a significant increase of pro-IL-1beta protein expression; NF-kappaB DNA binding activity; as well as IL-1beta and TNFalpha mRNA expression of the peritoneal macrophages in Nod2(2939iC) mice. Collectively, the increase of bacterial killing activity, IL-1beta expression, and NF-kappaB DNA binding activity of macrophages in Nod2(2939iC) mice suggests that NOD2 is a positive regulator of NF-kappaB/IL-1beta-mediated innate response to bacteria challenge in Crohn's disease.
Tsay
Tzyy-Bin
TB
Department of Surgery, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan.
Chang
Chien-Jen
CJ
Chen
Pei-Hsuan
PH
Hsu
Ching-Mei
CM
Chen
Lee-Wei
LW
D000818:Animals; D003424:Crohn Disease / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000502:physiology; D011550:Pseudomonas aeruginosa / Q000254:growth & development / Q000276:immunology*
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D053473:Nod2 Signaling Adaptor Protein