Corticosteroids repress the interleukin 1 beta-induced secretion of collagenase in human intestinal smooth muscle cells.
OBJECTIVE
The cytokine interleukin (IL)-1 beta induces collagenase expression and inhibits collagen expression in human intestinal smooth muscle (HISM) cells. Corticosteroids cause transrepression of certain genes, including the collagenase gene. The aim of this study was to determine if corticosteroids repress the induction of collagenase expression and the inhibition of collagen secretion by IL-1 beta in HISM cells.


METHODS
HISM cells were exposed to IL-1 beta (1-100 pmol/L) for 24 hours in the presence or absence of dexamethasone (10(-6) mol/L). Collagenase messenger RNA (mRNA) levels were determined by ribonuclease protection assay. Collagenase and tissue inhibitor of metalloproteinase protein secretion were determined by enzyme-linked immunosorbent assay of culture medium. Procollagen and collagen secretion were determined by polyacrylamide slab gel analysis of radiolabeled proteins in culture medium.


RESULTS
A 30-fold induction of collagenase mRNA and collagenase protein secretion by IL-1 beta was completely abrogated by dexamethasone. Dexamethasone at 10(-6) mol/L also reduced basal levels of collagenase mRNA by 50% and blocked the IL-1 beta-induced inhibition of collagen secretion.


CONCLUSIONS
Corticosteroids repress the collagenolytic action of IL-1 beta on HISM cells in vitro and therefore should promote healing in the inflamed intestine.
Graham
M F
MF
Department of Pediatrics, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA. mgraham@gems.vcu.edu
Willey
A
A
Zhu
Y N
YN
Yager
D R
DR
Sugerman
H J
HJ
Diegelmann
R F
RF
D003094:Collagen / Q000037:antagonists & inhibitors / Q000378:metabolism; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D005938:Glucocorticoids; D007375:Interleukin-1; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D003907:Dexamethasone; D003094:Collagen; D017364:Collagenases