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Gut-selective integrin-targeted therapies for inflammatory bowel disease.

08:00 EDT 15th May 2018 | BioPortfolio

Summary of "Gut-selective integrin-targeted therapies for inflammatory bowel disease."

Integrins are cell surface receptors with bi-directional signaling capabilities that can bind to adhesion molecules in order to mediate homing of leukocytes to peripheral tissues. Gut-selective leukocyte homing is facilitated by interactions between α4β7 and its ligand MAdCAM-1, while retention of lymphocytes in mucosal tissues is mediated by αEβ7 binding to its ligand E-cadherin. Therapies targeting gut-selective trafficking have shown efficacy in inflammatory bowel disease (IBD), confirming the importance of leukocyte trafficking in disease pathobiology. This review will provide an overview of integrin structure, function and signaling, and highlight the role that these molecules play in leukocyte homing and retention. Anti-integrin therapeutics, including gut-selective antibodies against the β7 integrin subunit (etrolizumab) and the α4β7 integrin heterodimer (vedolizumab and abrilumab), as well as the non-gut selective anti-α4 integrin (natalizumab), will be discussed as well as novel targeting approaches using small molecules.

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This article was published in the following journal.

Name: Journal of Crohn's & colitis
ISSN: 1876-4479
Pages:

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Medical and Biotech [MESH] Definitions

An anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed)

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An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.

An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.

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