Suppression of T cell-mediated injury in human gut by interleukin 10: role of matrix metalloproteinases

Gastroenterology. 1998 Sep;115(3):573-83. doi: 10.1016/s0016-5085(98)70136-2.


Background & aims: Activation of lamina propria T cells with pokeweed mitogen in human fetal gut explant cultures results in severe mucosal injury. In the same system, Staphylococcus aureus enterotoxin B produces villus atrophy and crypt cell hyperplasia. The aim of this study was to examine the ability of interleukin (IL)-10 to modify these changes.

Methods: Mucosal pathology and lamina propria glycosaminoglycans were assessed histologically, and CD3(+), CD25(+) and alpha-actin smooth muscle-positive cells were determined by immunohistochemistry. Reverse plaque assays and quantitative reverse-transcriptase polymerase chain reaction were used to analyze the cytokine response. Matrix metalloproteinase production was analyzed by Western blotting, in situ hybridization, and zymography.

Results: Both experimental enteropathies produced mucosal damage, although injury was greater after pokeweed mitogen activation than S. aureus enterotoxin B. In both cases, the increase in cytokine-secreting cells and transcripts observed after T-cell activation was inhibited by IL-10. IL-10 also inhibited the increase in collagenase and stromelysin-1 in the explant culture supernatants and the loss of glycosaminoglycans. IL-10 decreased metalloproteinase production in control explants and increased matrix. In mesenchymal cells, IL-10 had a minor effect on metalloproteinase production.

Conclusions: IL-10 down-regulates mucosal T-cell activation, metalloproteinase production, and loss of extracellular matrix and prevents mucosal damage in the gut.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / analysis
  • CD3 Complex / analysis
  • Collagenases / biosynthesis
  • Cytokines / biosynthesis*
  • Enterotoxins / toxicity
  • Fetus
  • Glycosaminoglycans / metabolism
  • Humans
  • Immunity, Mucosal
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interleukin-10 / pharmacology*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / pathology
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism*
  • Intestine, Small / pathology
  • Keratins / analysis
  • Lymphocyte Activation
  • Matrix Metalloproteinase 3 / biosynthesis
  • Mesoderm / drug effects
  • Mesoderm / enzymology
  • Mesoderm / pathology
  • Metalloendopeptidases / biosynthesis*
  • Metalloendopeptidases / genetics
  • Muscle, Smooth / embryology
  • Muscle, Smooth / metabolism
  • Organ Culture Techniques
  • Pokeweed Mitogens
  • Polymerase Chain Reaction
  • Receptors, Interleukin-2 / analysis
  • T-Lymphocytes / immunology*
  • Transcription, Genetic


  • Antigens, CD
  • CD3 Complex
  • Cytokines
  • Enterotoxins
  • Glycosaminoglycans
  • Pokeweed Mitogens
  • Receptors, Interleukin-2
  • Interleukin-10
  • enterotoxin B, staphylococcal
  • Keratins
  • Interferon-gamma
  • Collagenases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 3