Gliadin stimulates human monocytes to production of IL-8 and TNF-alpha through a mechanism involving NF-kappaB.
Wheat gliadin is the triggering agent in coeliac disease. In this study, we documented that proteolytic fragments of gliadin, in contrast to other food antigens, induced interleukin (IL)-8 and tumour necrosis factor-alpha (TNF-alpha) production and significantly increased interferon (IFN)-gamma-induced cytokine secretion in human monocytic line THP-1 cells. Stimulation with gliadin resulted in elevated phosphorylation of the IkappaBalpha molecule and increased NF-kappaB/DNA binding activity that was inhibited by sulfasalazine, l-1-tosylamido-2-phenylethyl chloromethyl ketone and pyrrolidine dithiocarbamate (PDTC). The activation pathway was shown to be independent of the CD14 molecule. Less mature U-937 monocytes responded to gliadin stimulation by low IL-8 secretion, TNF-alpha production was not detectable. We propose that gliadin-induced activation of monocytes/macrophages can participate in mechanisms leading to the impairment of intestinal mucosa in coeliac patients.
Jelínková
Lenka
L
Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague, Czech Republic. lenicka@biomed.cas.cz
Tucková
Ludmila
L
Cinová
Jana
J
Flegelová
Zuzana
Z
Tlaskalová-Hogenová
Helena
H
D000595:Amino Acid Sequence; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005903:Gliadin / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D010047:Ovalbumin / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D030262:Soybean Proteins / Q000494:pharmacology; D014908:Triticum; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D020298:U937 Cells
D016209:Interleukin-8; D016328:NF-kappa B; D010446:Peptide Fragments; D030262:Soybean Proteins; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin; D005903:Gliadin