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.
Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague, Czech Republic. lenicka@biomed.cas.cz
Lenka
L
Jelínková
Ludmila
L
Tucková
Jana
J
Cinová
Zuzana
Z
Flegelová
Helena
H
Tlaskalová-Hogenová
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