Carbon monoxide and heme oxygenase-1 prevent intestinal inflammation in mice by promoting bacterial clearance.
Carbon monoxide and heme oxygenase-1 prevent intestinal inflammation in mice by promoting bacterial clearance.
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DOI：
10.1053/j.gastro.2012.12.025
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发表时间：
2013-04
期刊：
影响因子：
29.4
通讯作者：
Plevy SE
中科院分区：
文献类型：
--
作者：
Onyiah JC;Sheikh SZ;Maharshak N;Steinbach EC;Russo SM;Kobayashi T;Mackey LC;Hansen JJ;Moeser AJ;Rawls JF;Borst LB;Otterbein LE;Plevy SE
血红素加氧酶 - 1（HO - 1）及其代谢副产物一氧化碳（CO）在结肠炎实验模型中对肠道炎症具有保护作用，但对其肠道免疫机制知之甚少。我们研究了小鼠和斑马鱼中CO、HO - 1和肠道微生物群之间的相互作用。
无菌、野生型和Il10 - / - 小鼠以及无菌斑马鱼胚胎用无病原体（SPF）进行定植。无菌或SPF饲养的野生型和Il10 - / - 小鼠腹腔注射钴原卟啉（CoPP，可上调HO - 1）、一氧化碳释放分子ALF186或生理盐水（对照）。在SPF条件下饲养的野生型小鼠通过感染鼠伤寒沙门氏菌诱发结肠炎。
在无菌野生型小鼠的结肠中，SPF微生物群通过激活Nrf2 - 、IL - 10 - 和 toll样受体依赖的途径诱导HO - 1的产生；在斑马鱼中也有类似观察结果。SPF微生物群不会在无菌Il10 - / - 小鼠的结肠中诱导HO - 1。在从无菌向SPF条件转变之前给Il10 - / - 小鼠施用CoPP可减少其结肠炎的发生。在Il10 - / - 小鼠中，CO和CoPP降低了肠系膜淋巴结（MLN）中肠道细菌基因组DNA的水平。在鼠伤寒沙门氏菌诱导的小肠结肠炎小鼠中，CoPP减少了从固有层、MLN、脾脏和肝脏中回收的活鼠伤寒沙门氏菌的数量。在小鼠巨噬细胞中敲低HO - 1会损害其对大肠杆菌、粪肠球菌和鼠伤寒沙门氏菌的杀菌活性，而暴露于CO或HO - 1的过表达则会增加其杀菌活性。HO - 1的诱导和CO增加了吞噬溶酶体的酸化。
结肠中的HO - 1可预防小鼠的结肠炎症。HO - 1由肠道微生物群诱导，其稳态功能部分通过促进巨噬细胞的杀菌活性来介导。
Heme oxygenase-1 (HO-1) and its metabolic by-product, carbon monoxide (CO), protect against intestinal inflammation in experimental models of colitis, but little is known about their intestinal immune mechanisms. We investigated the interactions among CO, HO-1, and the enteric microbiota in mice and zebrafish. Germ-free, wild-type, and Il10−/− mice and germ free zebrafish embryos were colonized with pathogen-free (SPF). Germ-free or SPF-raised wild-type and Il10−/− mice were given intraperitoneal injections of cobalt protoporphyrin (CoPP), which upregulates HO-1, the CO releasing molecule ALF186, or saline (control). Colitis was induced in wild-type mice housed in SPF conditions by infection with S. typhimurium. In colons of germ-free, wild-type mice, SPF microbiota induced production of HO-1 via activation of Nrf2–, IL-10–, and toll-like receptor–dependent pathways; similar observations were made in zebrafish. SPF microbiota did not induce HO-1 in colons of germ-free Il10−/− mice. Administration of CoPP to Il10−/− mice before transition from germ-free to SPF conditions reduced their development of colitis. In Il10−/− mice, CO and CoPP reduced levels of enteric bacterial genomic DNA in mesenteric lymph nodes (MLN). In mice with S. typhimurium-induced enterocolitis, CoPP reduced the numbers of live S. typhimurium recovered from the lamina propria, MLN, spleen, and liver. Knockdown of HO-1 in mouse macrophages impaired their bactericidal activity against E. coli, E. faecalis, and S. typhimurium, whereas exposure to CO or overexpression of HO-1 increased their bactericidal activity. HO-1 induction and CO increased acidification of phagolysosomes. Colonic HO-1 prevents colonic inflammation in mice. HO-1 is induced by the enteric microbiota and its homeostatic function is mediated, in part, by promoting bactericidal activities of macrophages.
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DOI：
10.1152/ajpgi.00304.2006
发表时间：
2007-08-01
影响因子：
4.5
作者：
Moeser, Adam J.;Ryan, Kathleen A.;Blikslager, Anthony T.
通讯作者：
Blikslager, Anthony T.
影响因子：
1.6
作者：
Otterbein, LE;May, A;Chin, BY
通讯作者：
Chin, BY
影响因子：
9.4
作者：
Horz, HP;Vianna, ME;Conrads, G
通讯作者：
Conrads, G
影响因子：
15.9
作者：
Chung, Su Wol;Liu, Xiaoli;Perrella, Mark A.
通讯作者：
Perrella, Mark A.
DOI：
10.1084/jem.20051047
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hegazi RA;Rao KN;Mayle A;Sepulveda AR;Otterbein LE;Plevy SE
通讯作者：
Plevy SE