Animal models of mucosal inflammation and their relation to human inflammatory bowel disease

Blumberg, Richard S.; Saubermann, Lawrence J.; Strober, Warren

doi:10.1016/s0952-7915(99)00032-1

Cited by 414 publications

(341 citation statements)

References 53 publications

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“…Acquired immune cells, especially CD4 + T cells, have a considerable ability to induce the development and exacerbation of not only CD-like, but also UClike experimental colitis [24][25][26][27] . Importantly, Takeda et al showed that T cell specific STAT3 knockout mice showed impaired T cell proliferation [19] .…”

Section: The Role Of Stat3 On Acquired Immune Cells In Ibdmentioning

confidence: 99%

Role of STAT3 in inflammatory bowel disease

Sugimoto¹

2008

WJG

111

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Signal transducers and activators of transcription 3 (STAT3) play an important role in various autoimmune disorders including inflammatory bowel disease (IBD). Recent studies have revealed that STAT3 activation plays distinctly different roles between innate immune responses and acquired immune responses in colitis. STAT3-mediated activation of acquired immune responses plays a pathogenic role in colitis by enhancing the survival of pathogenic T cells. In contrast, STAT3-mediated activation of innate responses contributes to the suppression of colitis. This review will summarize the current understanding of the roles of STAT3 in IBD and the potential of targeting STAT3 for the treatment of IBD, emphasizing recent observations.

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Section: The Role Of Stat3 On Acquired Immune Cells In Ibdmentioning

confidence: 99%

Role of STAT3 in inflammatory bowel disease

Sugimoto¹

2008

WJG

111

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“…Second, manipulation of the bacterial flora either through the use of antibiotics or probiotics is effective in ameliorating inflammatory bowel disease (16 -21). Finally, over 30 animal models have been described that mimic human inflammatory bowel disease (22). In general, these animals do not develop intestinal inflammation in the absence of commensal bacteria (23)(24)(25)(26)(27)(28).…”

Section: Human Intestinal Epithelial Cells Are Broadly Unresponsive Tmentioning

confidence: 99%

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

Melmed¹,

Thomas²,

Lee³

et al. 2003

The Journal of Immunology

395

281

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Intestinal epithelial cells (IEC) interact with a high density of Gram-positive bacteria and are active participants in mucosal immune responses. Recognition of Gram-positive organisms by Toll-like receptor (TLR)2 induces proinflammatory gene expression by diverse cells. We hypothesized that IEC are unresponsive to Gram-positive pathogen-associated molecular patterns and sought to characterize the functional responses of IEC to TLR2-specific ligands. Human colonic epithelial cells isolated by laser capture microscopy and IEC lines (Caco-2, T84, HT-29) were analyzed for expression of TLR2, TLR6, TLR1, and Toll inhibitory protein (Tollip) mRNA by RT-PCR and quantitative real-time PCR. Response to Gram-positive bacterial ligands was measured by NF-κB reporter gene activation and IL-8 secretion. TLR2 protein expression was analyzed by immunofluorescence and flow cytometry. Colonic epithelial cells and lamina propria cells from both uninflamed and inflamed tissue demonstrate low expression of TLR2 mRNA compared with THP-1 monocytes. IECs were unresponsive to TLR2 ligands including the staphylococcal-derived Ags phenol soluble modulin, peptidoglycan, and lipotechoic acid and the mycobacterial-derived Ag soluble tuberculosis factor. Transgenic expression of TLR2 and TLR6 restored responsiveness to phenol soluble modulin and peptidoglycan in IEC. In addition to low levels of TLR2 protein expression, IEC also express high levels of the inhibitory molecule Tollip. We conclude that IEC are broadly unresponsive to TLR2 ligands secondary to deficient expression of TLR2 and TLR6. The relative absence of TLR2 protein expression by IEC and high level of Tollip expression may be important in preventing chronic proinflammatory cytokine secretion in response to commensal Gram-positive bacteria in the gut.

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“…However, since steroid therapy causes remission of IBD, it is believed that T cells play a critical role in the progression of IBD [1]. In most human cases examined, IBD is associated with a type 1 helper T cell (Th1) response [2]. Most interestingly, IBD also requires the presence of phagocytic cells such as monocytes, macrophages and neutrophils [3,4].…”

Section: Introductionmentioning

confidence: 99%

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

Shi

Das

2006

Cell Res

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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.

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Animal models of mucosal inflammation and their relation to human inflammatory bowel disease

Cited by 414 publications

References 53 publications

Role of STAT3 in inflammatory bowel disease

Role of STAT3 in inflammatory bowel disease

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

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

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