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New Gliadin Peptide Plays a Key Role in Celiac Disease


New research on gliadin peptide and celiac disease. Photo: Microscope - CC - Sarah_G

Celiac.com 03/09/2011 - A team of researchers recently identified a novel immunomodulatory gliadin peptide that triggers interleukin-8 release in a chemokine receptor CXCR3-dependent manner only in patients with celiac disease.

The research team included Karen M. Lammers; Sunaina Khandelwal; Fatima Chaudhry; Debby Kryszak; Elaine L. Puppa; Vincenzo Casolaro; and Alessio Fasano.

The same research team had previously reported that the chemokine receptor CXCR3 serves as a receptor for specific gliadin peptides that trigger zonulin release and increase in intestinal permeability.

This mechanism plays an important role in the adverse immune reaction to gluten-containing grains that is central to the classic celiac disease response.

To examine the role of CXCR3 in the immune response to gliadin, the researchers incubated peripheral blood mononuclear cells of both celiac patients and healthy controls with either pepsin-trypsin-digested gliadin or 11 α-gliadin synthetic peptides in the presence or absence of a blocking anti-CXCR3 monoclonal antibody.

The team then analyzed supernatants for interleukin-6 (IL-6), IL-8, IL-10, IL-13, IP-10 (CXCL10), tumour necrosis factor-α and interferon-γ.

Gliadin triggered cytokine production regardless of clinical condition. However, only small number of individuals showed IL-8 production. In those individuals, cells originating from white blood cells were the main source of IL-8 production.

The team used one of a comprehensive panel of synthetic α-gliadin peptides to reproduce the induction of IL-8.

They were able to cease the process by blocking CXCR3 before stimulation with either gliadin or this peptide in the celiac group, but not in the control group.

This suggests that gliadin-induced IL-8 production is CXCR3-dependent only in people with celiac disease.

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