Inflammatory bowel disease requires the interplay between innate and adaptive immune signals.
Inflammatory bowl disease (IBD) is a type 1 T helper cell (Th1)-mediated autoimmune disease. Various studies have revealed that environmental pathogens also play a significant role in the initiation and progression of this disease. Interestingly, the pathogenesis of IBD has been shown to be related to nitric oxide (NO) released from innate immune cells. Although NO is known to be highly toxic to the gut epithelia, there is very little information about the regulation of NO production, One major question in the etiology of IBD is how Th1 cells and pathogens interact in the induction of IBD. In present study, we focused on the regulation of NO. We show that macrophages require both interferon-gamma (IFN-gamma)-mediated and TLR4-mediated signals for the production of NO, which causes inflammation in the intestine and subsequently IBD. Thus, IBD is the result of concerted actions of innate immune signals, such as the binding of LPS to TLR-4, and adaptive immune signals, such as IFN-gamma produced by Th1 cells.
Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 661 Hoes Lane, Piscataway, 08854, USA.
Dayna
D
Shi
Jyoti
J
Das
Gobardhan
G
Das
D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D018398:Homeodomain Proteins / Q000235:genetics; D007113:Immunity, Innate; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000276:immunology*; D007371:Interferon-gamma; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D018417:Th1 Cells / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014302:Trinitrobenzenesulfonic Acid; D019323:omega-N-Methylarginine / Q000494:pharmacology
D018398:Homeodomain Proteins; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; C064658:RAG-1 protein; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid