Study of tumor necrosis factor receptor in the inflammatory bowel disease

Author(s)

Souza, Roberta Figueiroa ; Caetano, Marcos Antonio Ferreira ; Magalhaes, Henrique Inhauser Riceti ; Castelucci, Patricia

• Document type: Journal article
• Source: WORLD JOURNAL OF GASTROENTEROLOGY; v. 29, n. 18, p. 14-pg., 2023-05-14.

Abstract

Ulcerative colitis (UC) and Crohn's disease (CD) are part of Inflammatory Bowel Diseases (IBD) and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells. In addition, the main inflammatory mediator is related to the tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a mediator of the intestinal inflammatory processes, thus being one of the main cytokines involved in the pathogenesis of IBD, however, its levels, when measured, are present in the serum of patients with IBD. In addition, TNF-alpha plays an important role in promoting inflammation, such as the production of interleukins (IL), for instance IL-1 beta and IL-6. There are two receptors for TNF as following: The tumor necrosis factor 1 receptor (TNFR1); and the tumor necrosis factor 2 receptor (TNFR2). They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity. The soluble TNF form binds to the TNFR1 receptor with, and its activation results in a signaling cascade effects such as apoptosis, cell proliferation and cytokine secretion. In contrast, the transmembrane TNF form can bind both to TNFR1 and TNFR2. Recent studies have suggested that TNF-alpha is one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD, since TNF levels are present in the serum of both patients with UC and CD. Intravenous and subcutaneous biologics targeting TNF-alpha have revolutionized the treatment of IBD, thus becoming the best available agents to induce and maintain IBD remission. The application of antibodies aimed at neutralizing TNF- a in patients with IBD that induce a satisfactory clinical response in up to 60% of patients, and also induced long-term maintenance of disease remission in most patients. It has been suggested that anti-TNF-alpha agents inactivate the pro-inflammatory cytokine TNF-alpha by direct neutralization, i. e., resulting in suppression of inflammation. However, anti-TNF-alpha antibodies perform more complex functions than a simple blockade. (AU)

• FAPESP's process: 18/07862-1 - Study of the effect of experimental ulcerative colitis on the enteric nervous system of P2X7 receptor deficient mice (P2X7-/-)
• Grantee: Patricia Castelucci
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/25927-2 - Morphological, molecular and functional aspects of the interaction between the P2X7 receptor and pannexin-1 in the enteric glial cells following intestinal ischemia/reperfusion
• Grantee: Patricia Castelucci
• Support Opportunities: Regular Research Grants