To elucidate the role of innate immune responses in celiac disease, we investigated the effect of gliadin on blood monocytes from patients with celiac disease. Gliadin induced substantial TNF-α and IL-8 production by monocytes from patients with active celiac disease, lower levels by monocytes from patients with inactive celiac disease, and even lower levels by monocytes from healthy donors. In healthy donor monocytes gliadin induced IL-8 from monocytes expressing HLA-DQ2 and increased monocyte expression of the costimulatory molecules CD80 and CD86, the dendritic cell marker CD83, and the activation marker CD40. Gliadin also increased DNA binding activity of NF-κB p50 and p65 subunits in monocytes from celiac patients, and NF-κB inhibitors reduced both DNA binding activity and cytokine production. Thus, gliadin activation of HLA-DQ2+ monocytes leading to chemokine and proinflammatory cytokine production may contribute to the host innate immune response in celiac disease.
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ACKNOWLEDGMENTS
This work was supported by the Grant Agency of the Czech Republic (Grants 310/05/2245 and 310/03/H147); the Grant Agency of the Czech Academy of Sciences (Grants AA5020210, AA5020205, 1QS500200572, and B5020407); the Grant Agency of the Ministry of Education (MSM 0021620814, GA UK 30/2006), Mininstry of Agriculture 1B53002 and Institutional Research Concept (Grant AV0Z50200510); and the National Institutes of Health (U.S.) (DK-74033, DK-47322, DK-54495, HD-41361, and DK-064400); the Crohn’s and Colitis Foundation of America; and the Research Service of the Veterans Administration
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CINOVA, J., PALOVÁ-JELÍNKOVÁ, L., SMYTHIES, L. et al. Gliadin Peptides Activate Blood Monocytes from Patients with Celiac Disease. J Clin Immunol 27, 201–209 (2007). https://doi.org/10.1007/s10875-006-9061-z
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DOI: https://doi.org/10.1007/s10875-006-9061-z