Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway
Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway
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DOI：
10.1038/74680
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发表时间：
2000-04-01
期刊：
影响因子：
82.9
通讯作者：
Choi, AMK
中科院分区：
文献类型：
--
作者：
Otterbein, LE;Bach, FH;Choi, AMK
应激诱导蛋白血红素加氧酶 - 1可抵御氧化应激。血红素加氧酶 - 1的抗炎特性可能是这种细胞保护作用的基础。在此我们证明，一氧化碳（血红素加氧酶分解血红素的一种副产物）具有强大的抗炎作用。在体内和体外，低浓度的一氧化碳有差异且选择性地抑制脂多糖诱导的促炎细胞因子肿瘤坏死因子 -α、白细胞介素 - 1β和巨噬细胞炎性蛋白 - 1β的表达，并增加脂多糖诱导的抗炎细胞因子白细胞介素 - 10的表达。一氧化碳并非通过鸟苷酸环化酶 - cGMP或一氧化氮途径，而是通过涉及丝裂原活化蛋白激酶的途径介导这些抗炎作用。这些数据表明，一氧化碳在炎症性疾病状态中可能具有重要的保护功能，因此具有潜在的治疗用途。
The stress-inducible protein heme oxygenase-1 provides protection against oxidative stress. The antiinflammatory properties of heme oxygenase-1 may serve as a basis for this cytoprotection. We demonstrate here that carbon monoxide, a by-product of heme catabolism by heme oxygenase, mediates potent anti-inflammatory effects. Both in vivo and in vitro, carbon monoxide at low concentrations differentially and selectively inhibited the expression of lipopolysaccharide-induced pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, and macrophage inflammatory protein-lp and increased the lipopolysaccharide-induced expression of the anti-inflammatory cytokine interleukin-10. Carbon monoxide mediated these anti-inflammatory effects not through a guanylyl cyclase-cGMP or nitric oxide pathway, but instead through a pathway involving the mitogen-activated protein kinases. These data indicate the possibility that carbon monoxide may have an important protective function in inflammatory disease states and thus has potential therapeutic uses.