IL-1 regulates in vivo C-X-C chemokine induction and neutrophil sequestration following endotoxemia
IL-1 regulates in vivo C-X-C chemokine induction and neutrophil sequestration following endotoxemia
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DOI：
10.1179/096805102125000092
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发表时间：
2002-01-01
期刊：
影响因子：
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通讯作者：
McIntyre, RC
中科院分区：
文献类型：
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作者：
Calkins, CM;Bensard, DD;McIntyre, RC
中性粒细胞响应炎症刺激而流入组织涉及C-X-C趋化因子。白细胞介素-I（IL-1）在体外刺激趋化因子产生，但其在体内对趋化因子产生的作用尚不清楚。我们假设IL-1介导了由全身性脂多糖（LPS）诱导的体内组织C-X-C趋化因子的产生。IL-1活性可被IL-1受体拮抗剂（IL-1 Ra）阻断。给大鼠注射沙门氏菌属（Salmonella），φ LPS（0.5mg/kg），预先给予和不给予IL-1 Ra。测定细胞因子诱导的中性粒细胞趋化因子-1（CINC-1）和巨噬细胞炎性蛋白-2（MIP-2）蛋白和mRNA水平、组织中性粒细胞蓄积和器官损伤指数。LPS给药导致血浆、肺和肝脏IL-1 β增加，而IL-1 Ra降低。LPS还诱导血浆、肺和肝CINC-1和MIP-2蛋白和mRNA的增加。然而，IL-1 Ra对LPS诱导的血浆或肺组织CINC-1水平没有影响。相反，与LPS处理的对照相比，IL-1 Ra预处理显著降低了肝脏中的CINC-1蛋白表达（降低45%）和血浆中的MIP-2蛋白表达（降低100%）、肺（降低72%）和肝脏（降低100%）。通过北方印迹分析，肺和肝中CINC-1和MIP-2的稳态mRNA水平与蛋白质结果相似。用IL-1 Ra预处理还导致LPS后肺和肝中性粒细胞积聚分别减少47%和59%。此外，在用IL-1 Ra预处理的动物中，肺和肝损伤的指数均降低。总之，LPS诱导肺和肝中的IL-1 β和MIP-2表达，这两者都是IL-1依赖性的。尽管LPS后肺和肝中的肺中性粒细胞积聚也是IL-1介导的，但肺CINC-1水平不受IL-1 Ra的影响。这些数据表明IL-1调节LPS后组织趋化因子表达和中性粒细胞积聚。
The influx of neutrophils into tissues in response to inflammatory stimuli involves C-X-C chemokines. Interleukin-l (IL-1) stimulates chemokine production in vitro, but its role in vivo on chemokine production is not as clearly understood. We hypothesized that IL-1 mediates in vivo tissue C-X-C chemokine production induced by systemic lipopolysaccharide (LPS). IL-1 activity was blocked by IL-1 receptor antagonist (IL-1Ra). Rats were injected with Salmonella,)phi LPS (0.5 mg/kg) with and without prior administration of IL-1Ra. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage inflammatory protein-2 (MIP-2) protein and mRNA levels, tissue neutrophil accumulation, and indices of organ injury were measured. LPS administration resulted in increased plasma, lung, and liver IL-1beta that was decreased by IL-1Ra. LPS also induced an increase in plasma, lung, and liver CINC-1 and MIP-2 protein and mRNA. However, IL-1Ra had no effect on LPS-induced plasma or lung tissue CINC-1 levels. In contrast, IL-1Ra pretreatment did significantly decrease CINC-1 protein expression in the liver (45% decrease) and MIP-2 protein expression in plasma (100% decrease), lung (72% decrease) and liver (100% decrease) compared to LPS-treated controls. Steady-state mRNA levels by Northern blot analysis of both CINC-1 and MIP-2 in lung and liver were similar to the protein findings. Pretreatment with IL-1Ra also resulted in a 47% and 59% decrease in lung and liver neutrophil accumulation, respectively, following LPS. In addition, indices of both lung and liver injury were decreased in animals pretreated with IL-1Ra. In summary, LPS induces IL-1beta and MIP-2 expression in the lung and liver, both of which are IL-1 dependent. Although lung neutrophil accumulation in both lung and liver after LPS is also IL-1 mediated, lung CINC-1 levels were unaffected by IL-1Ra. These data suggest that IL-1 regulates tissue chemokine expression and neutrophil accumulation after LPS.