Enteric flora and lymphocyte-derived cytokines determine expression of heat shock proteins in mouse colonic epithelial cells
Enteric flora and lymphocyte-derived cytokines determine expression of heat shock proteins in mouse colonic epithelial cells
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DOI：
10.1016/s0016-5085(03)00215-4
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发表时间：
2003-05-01
期刊：
影响因子：
29.4
通讯作者：
Chang, EB
中科院分区：
文献类型：
--
作者：
Kojima, K;Musch, MW;Chang, EB
背景与目的：诱导性热休克蛋白（hsps），特别是hsp25和hsp72，在肠上皮细胞表面表达，可能具有保护肠上皮细胞免受损伤的作用。本研究旨在确定肠道细菌和/或免疫信号是否调节其生理表达。方法：研究免疫缺陷小鼠（-/-）和正常小鼠肠道hsp25、hsp72和组成型hsc73的表达。采用甘露醇通量法和经上皮阻力法测定粘膜通透性。用重组细胞因子、活化的固有层淋巴细胞（LPLs）或脆弱拟杆菌（Bacteroides fragilis）孵育小肠YAMC细胞，评估热休克蛋白在YAMC细胞中的表达。结果：慢性甲硝唑治疗减少；hsp25和hsp72的表达与粘膜屏障功能对艰难梭菌毒素的易感性增加有关。在脆弱芽孢杆菌孵育的YAMC细胞中，Hsp的表达也增加，这一作用由脂多糖和其他细菌源性因素介导。RAG-1（-/-）小鼠结肠hsp72表达降低，但hsp25或hsc73表达不降低。重组IL-2和其他细胞因子增强YAMC hsp25和/或hsp72的表达。活化的LPLs诱导YAMC hsp表达，该作用被IL-2中和抗体阻断。结论：肠道菌群和粘膜淋巴细胞在维持结肠菌hsp25和hsp72的生理性表达中发挥作用。
Background & Aims: Inducible heat shock proteins (hsps), particularly hsp25 and hsp72, are expressed by surface colonocytes and may have a role in protecting intestinal epithelial cells against injury. This study is aimed at determining if enteric bacteria and/or immune signals regulate their physiologic expression. Methods: Intestinal hsp25, hsp72, and constitutive hsc73 expression were studied in immunodeficient RAG-1(-/-) mice and in normal mice. Mucosal permeability was measured by mannitol flux and transepithelial resistance. Hsp expression in intestinal YAMC cells was assessed after incubation with recombinant cytokines, activated lamina propria lymphocytes (LPLs), or Bacteroides fragilis. Results: Chronic metronidazole treatment decreases; colonic mucosal hsp25 and hsp72 expression, an effect associated with increased susceptibility of mucosal barrier function to C. difficile toxin A. Hsp expression also was increased in YAMC cells incubated with B. fragilis, an effect mediated by lipopolysaccharide and other bacteria-derived factors. Colonic hsp72, but not hsp25 or hsc73, expression is decreased in RAG-1(-/-) mice. Recombinant IL-2 and other cytokines enhance YAMC hsp25 and/or hsp72 expression. Activated LPLs induce YAMC hsp expression, an effect blocked by IL-2 neutralizing antibody. Conclusions: Enteric flora and mucosal lymphocytes play a role in maintaining physiologic expression of colonocyte hsp25 and hsp72.