Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine

Savidge, Tor; Pan, Weihua; Newman, Paul; O’Brien, Michael; Anton, Pauline M.; Pothoulakis, Charalabos

doi:10.1016/s0016-5085(03)00902-8

Cited by 204 publications

(163 citation statements)

References 40 publications

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“…We previously reported (26) that epithelial cells in the grafted intestine are exclusively of human origin and that injection of toxin A induces an acute inflammatory response, similar to that seen in animal models and in the colon of patients with C. difficile-associated colitis. We found no expression of COX-2 in control xenografts, but robust increases of COX-2 expression 6 h after toxin A exposure (Fig.…”

Section: Induction Of Cox-2 By C Difficile Toxin a In Colonocytes-mentioning

confidence: 61%

“…difficile Toxin A-Toxin A and toxin B were purified from culture supernatants of C. difficile strain VPI 10463 (American Type Culture Collection, Rockville, MD) using anion exchange chromatography and fast protein liquid chromatography as previously described (13,26).…”

Section: Methodsmentioning

confidence: 99%

“…Because toxin B also elicits inflammatory and cytotoxic responses in human colon in vitro (10) and in vivo (26), we also examined whether it is also able to stimulate COX-2 expression in these cells. We found that toxin A, but not toxin B, induced COX-2 expression at both mRNA and protein levels through ROS-mediated activation of p38 MAPK, mitogen-and stress-activated protein kinase-1 (MSK-1), ATF-1, and CREB.…”

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confidence: 99%

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Clostridium difficile Toxin A Regulates Inducible Cyclooxygenase-2 and Prostaglandin E2 Synthesis in Colonocytes via Reactive Oxygen Species and Activation of p38 MAPK

Kim

Rhee

Kokkotou

et al. 2005

Journal of Biological Chemistry

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Section: Induction Of Cox-2 By C Difficile Toxin a In Colonocytes-mentioning

confidence: 61%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Clostridium difficile Toxin A Regulates Inducible Cyclooxygenase-2 and Prostaglandin E2 Synthesis in Colonocytes via Reactive Oxygen Species and Activation of p38 MAPK

Kim

Rhee

Kokkotou

et al. 2005

Journal of Biological Chemistry

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118

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“…Hence, to examine epithelial cell expression of MCH and its receptors, we used a laser capture microdissection (LCM) approach to isolate colonic epithelial cells from cryopreserved surgical specimens obtained from patients with IBD and controls (35). Real-time RT-PCR analysis indicated that human colonic epithelial cells express MCHR1 (Fig.…”

Section: Mch Functional Receptors Are Expressed In Colonocytesmentioning

confidence: 99%

Melanin-concentrating hormone as a mediator of intestinal inflammation

Kokkotou¹,

Moss²,

Torres³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Melanin-concentrating hormone (MCH) is expressed primarily in the hypothalamus and has a positive impact on feeding behavior and energy balance. Although MCH is expressed in the gastrointestinal tract, its role in this system remains elusive. We demonstrate that, compared to wild type, mice genetically deficient in MCH had substantially reduced local inflammatory responses in a mouse model of experimental colitis induced by intracolonic administration of 2,4,6 trinitrobenzene sulfonic acid (TNBS). Likewise, mice receiving treatments with an anti-MCH antibody, either prophylactically or after the establishment of colitis, developed attenuated TNBS-associated colonic inflammation and survived longer. Consistent with a potential role of MCH in intestinal pathology, we detected increased colonic expression of MCH and its receptor in patients with inflammatory bowel disease. Moreover, we found that human colonic epithelial cells express functional MCH receptors, the activation of which induces IL-8 expression. Taken together, these results clearly implicate MCH in inflammatory processes in the intestine and perhaps elsewhere.experimental colitis ͉ IL-8 ͉ inflammatory bowel disease ͉ neuropeptides ͉ MCH deficient mice M elanin-concentrating hormone (MCH) is a 17-to 19-aa cyclic neuropeptide conserved from fish to human (1) and predominantly localized in the brain (2). Several pharmacological and genetic studies revealed a role for this peptide in the regulation of feeding behavior and energy expenditure toward a positive energy balance (3-5). More recent studies extended the physiological functions of MCH as a broad regulator of cognitive and autonomic aspects related to rewarding behaviors (6, 7). Outside the brain, MCH is localized in the pancreas (8), skin (9), and gastrointestinal tract (10). It has been also found in tissular and circulating immune cells (11)(12)(13)(14). However, the physiological role of MCH in these peripheral tissues has yet to be established.In humans, two G-protein-coupled receptors for MCH have been identified, MCHR1 (also known as SLC1 or GPR24) (15-18) and MCHR2 (19-21), whereas rodents express only MCHR1. In the rodent brain, MCHR1 is expressed in areas important for feeding, learning and motivated behavior, integration of sensory and gustatory inputs, autonomic control, and arousal (22, 23). MCHR1 mRNA is also expressed in the thyroid, kidney, adipose tissue, lung, testes, and tongue (23), whereas functional MCHR1 is also present in lymphocytes (12,14), insulin-producing cell lines (24), and mouse and human pancreatic islets (8).Several neuropeptides that are part of the neuroendocrine system exhibit important immunomodulatory effects and mediate inflammation in various organs, including the intestine (25, 26). There is little evidence to indicate expression of MCHR of either type in the intestine of animals or humans, and the role of MCH in inflammatory responses in the gut or elsewhere has not been evaluated. Based on these considerations and because MCH is also expressed in immune c...

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“…Several reports of the in vivo effects of TcdA in animal models reflect efforts to understand the cellular mechanism leading to clinical symptoms as well as to the release of mediators that are involved in the inflammatory process (2,13,15,18,20). The inherent glucosyltransferase…”

mentioning

confidence: 99%

Application of Mutated Clostridium difficile Toxin A for Determination of Glucosyltransferase-Dependent Effects

et al. 2006

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Mutation of tryptophan-101 in Clostridium difficile toxin A, a 308-kDa glucosyltransferase, resulted in a 50-fold-reduced cytopathic activity in cell culture experiments. The mutant toxin A was characterized and applied to distinguish between glucosyltransferase-dependent and -independent effects with respect to RhoB up-regulation as a cellular stress response.Clostridium difficile toxins A and B (TcdA and TcdB, respectively) are the major pathogenicity factors that are causative for antibiotic-associated pseudomembranous colitis (19). Several reports of the in vivo effects of TcdA in animal models reflect efforts to understand the cellular mechanism leading to clinical symptoms as well as to the release of mediators that are involved in the inflammatory process (2,13,15,18,20). The inherent glucosyltransferase

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Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine

Cited by 204 publications

References 40 publications

Clostridium difficile Toxin A Regulates Inducible Cyclooxygenase-2 and Prostaglandin E2 Synthesis in Colonocytes via Reactive Oxygen Species and Activation of p38 MAPK

Clostridium difficile Toxin A Regulates Inducible Cyclooxygenase-2 and Prostaglandin E2 Synthesis in Colonocytes via Reactive Oxygen Species and Activation of p38 MAPK

Melanin-concentrating hormone as a mediator of intestinal inflammation

Application of Mutated Clostridium difficile Toxin A for Determination of Glucosyltransferase-Dependent Effects

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