Interleukin 1 beta down-regulates collagen and augments collagenase expression in human intestinal smooth muscle cells.
OBJECTIVE
Smooth muscle cells resident in the intestinal wall play a significant role in the healing of the injured intestine and in the fibrosis that complicates Crohn's disease. The cytokine interleukin 1 beta (IL-1 beta) is involved in inflammatory bowel disease. The aim of this study was to determine the action of IL-1 beta on proliferation and collagen metabolism in human intestinal smooth muscle cells.


RESULTS
IL-beta caused a three-fold increase in [3H]thymidine uptake at 100 pmol/L. This mitogenic effect was equipotent with that of platelet-derived growth factor when cells were exposed to IL-beta for 48 vs. 24 hours. IL-beta inhibited the secretion of procollagen into culture medium by 70% and the accumulation of newly synthesized procollagen in cells by 55%. In addition, IL-beta caused a concentration-dependent inhibition of steady-state levels of procollagen I and III messenger RNA (85% inhibition at 100 pmol/L) and a 3-5-fold augmentation of collagenase messenger RNA levels.


CONCLUSIONS
IL-beta is mitogenic for human intestinal smooth muscle cells, but this action is associated with a concomitant down-regulation of collagen synthesis and secretion and an augmention of collagenase expression.
Graham
M F
MF
Department of Pediatrics and Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA. MGRAHAM@gems.vcu.edu.
Willey
A
A
Adams
J
J
Yager
D
D
Diegelmann
R F
RF
D015152:Blotting, Northern; D002455:Cell Division; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D011347:Procollagen; D012333:RNA, Messenger; D003094:Collagen; D017364:Collagenases