Gliadin stimulates human monocytes to production of IL-8 and TNF-alpha through a mechanism involving NF-kappaB

FEBS Lett. 2004 Jul 30;571(1-3):81-5. doi: 10.1016/j.febslet.2004.06.057.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Enzyme-Linked Immunosorbent Assay
  • Gliadin / pharmacology*
  • Humans
  • Interleukin-8 / biosynthesis*
  • Kinetics
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Monocytes / physiology
  • NF-kappa B / metabolism*
  • Ovalbumin / pharmacology
  • Peptide Fragments / pharmacology
  • Soybean Proteins / pharmacology
  • Triticum
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • U937 Cells


  • Interleukin-8
  • NF-kappa B
  • Peptide Fragments
  • Soybean Proteins
  • Tumor Necrosis Factor-alpha
  • Ovalbumin
  • Gliadin