Graham M F, Willey A, Zhu Y N, Yager D R, Sugerman H J, Diegelmann R F
Department of Pediatrics, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.
Gastroenterology. 1997 Dec;113(6):1924-9. doi: 10.1016/s0016-5085(97)70012-x.
BACKGROUND & AIMS: 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.
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.
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.
Corticosteroids repress the collagenolytic action of IL-1 beta on HISM cells in vitro and therefore should promote healing in the inflamed intestine.
细胞因子白细胞介素（IL）-1β可诱导人肠道平滑肌（HISM）细胞中胶原酶表达并抑制胶原蛋白表达。皮质类固醇可导致某些基因的反式抑制，包括胶原酶基因。本研究的目的是确定皮质类固醇是否会抑制IL-1β对HISM细胞中胶原酶表达的诱导作用以及对胶原蛋白分泌的抑制作用。
将HISM细胞在存在或不存在地塞米松（10⁻⁶mol/L）的情况下，暴露于IL-1β（1 - 100 pmol/L）24小时。通过核糖核酸酶保护试验测定胶原酶信使核糖核酸（mRNA）水平。通过对培养基进行酶联免疫吸附测定来确定胶原酶和金属蛋白酶组织抑制剂的蛋白质分泌。通过对培养基中放射性标记蛋白质进行聚丙烯酰胺平板凝胶分析来确定前胶原和胶原蛋白的分泌。
地塞米松完全消除了IL-1β对胶原酶mRNA和胶原酶蛋白分泌的30倍诱导作用。10⁻⁶mol/L的地塞米松还使胶原酶mRNA的基础水平降低了50%，并阻断了IL-1β诱导的对胶原蛋白分泌的抑制作用。
皮质类固醇在体外可抑制IL-1β对HISM细胞的胶原分解作用，因此应能促进炎症肠道的愈合。
