Abstract
HISM cell collagen production appears to play a major role in the pathogenesis of intestinal strictures in Crohn's disease. HISM cells in culture produce large amounts of collagen in the presence of fetal bovine serum (FBS). To determine the role of cAMP in the regulation of this collagen production, HISM cells were isolated from normal human jejunum, grown in culture and exposed to cholera toxin (CT, 10 ng/ml), isobutylmethylxanthine (IBMX, 0.16 mM) and CT + IBMX for 48 hours. Collagen synthesis was determined by the incorporation of 3H proline into collagenase-sensitive protein. CT and IBMX caused significant reductions in collagen synthesis and non-collagen protein synthesis (NCP). The inhibitory effects of CT and IBMX alone were selective for collagen as evidenced by significant reductions in relative collagen synthesis (RCS).
CT, IBMX and CT + IBMX caused a 3.5, 3 and 33 fold increase in HISM cell cAMP levels respectively. Increased cAMP levels down-regulate collagen synthesis by HISM cells. This response is most selective for collagen synthesis with smaller elevations in CAMP. Supported by NIH grants AMO7718, AM34151 and the N.F.I.C.
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Perr, H., Graham, M. & Diegelmann, R. CYCLIC AMP SUPPRESSES COLLAGEN SYNTHESIS BY HUMAN INTESTINAL SMOOTH MUSCLE (HISM) CELLS. Pediatr Res 21 (Suppl 4), 275 (1987). https://doi.org/10.1203/00006450-198704010-00646
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DOI: https://doi.org/10.1203/00006450-198704010-00646