Inflammatory bowel disease requires the interplay between innate and adaptive immune signals

Abstract

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-γ (IFN-γ)-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-γ produced by Th1 cells.

Increased colonic inflammatory injury and formation of aberrant crypt foci in Nrf2‐deficient mice upon dextran sulfate treatment

“…37,38 In the present study, the presence of an active Nrf2 pathway completely inhibited DSS-mediated proinflammatory cytokine signaling in the colon, whereas the lack of an active Nrf2 pathway resulted in significantly increased colonic proinflammatory signaling after exposure to DSS. Addi- tionally, increased levels of colonic biomarkers of inflammation were detected in N0 but not WT mice after DSS exposure potentially because of the decreased colonic proinflammatory stimulus, represented by decreased cytokine expression, present in WT but not N0 mice.…”

Differentiation of C2D Macrophage Cells after Adoptive Transfer

“…There is a tight interaction between the signaling pathways of TLR4 and IFN-␥ (11,16,62), and it was expected that there would be a significant impact on macrophage phenotype in the absence of TLR4. However, C2D macrophage cells transcribe their own TLR4 if it is needed for activation and thus may respond independently of host expression.…”

Anti-inflammatory and Immunomodulatory Properties of 2-Amino-3H-phenoxazin-3-one

“…Th1 cell-derived IFN-g stimulates regional macrophage or colonic epithelial cell activation and NO activation, which then leads to tissue destruction. [30][31][32] APO-induced inhibition of NO production was not restricted to macrophages stimulated by bacterial toxin LPS and/or IFN-g. TNF-a stimulates osteoblasts to secrete bone resorbing cytokines (IL-1b and IL-6) and NO that act directly on osteoclasts to cause bone resorption. 33) We examined the effect of APO on NO production by the murine osteoblast-like cell line MC3T3-E1 in response to TNF-a and IL-1b.…”