IL-10 is a central regulator of cyclooxygenase-2 expression and prostaglandin production
IL-10 is a central regulator of cyclooxygenase-2 expression and prostaglandin production
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DOI：
10.4049/jimmunol.166.4.2674
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发表时间：
2001-02-15
影响因子：
4.4
通讯作者：
Moore, SA
中科院分区：
文献类型：
--
作者：
Berg, DJ;Zhang, J;Moore, SA
IL-10是一种有效的抗炎和免疫调节细胞因子，当用LPS刺激时，IL-10（-/-）小鼠产生过量的炎性细胞因子，表明内源性IL-10是体内炎性细胞因子产生的中心调节因子。PG是脂质介质，在炎症反应期间也大量产生。为了研究IL-10在急性炎症反应期间调节PG产生的作用，我们评估了野生型（wt）和IL-10（-/-）小鼠中LPS诱导的环氧合酶（考克斯）表达和PC产生。LPS诱导的IL-10（-/-）脾细胞产生的PGE_3是野生型脾细胞的5.6倍。LPS刺激导致WT和IL-10（-/-）脾细胞中考克斯-2 mRNA和蛋白的诱导;然而，IL-10（-/-）小鼠中考克斯-2 mRNA的增加幅度是WT小鼠的5.5倍。在wt或IL-10-/小鼠中，COX-I蛋白水平不受LPS刺激的影响。IFN-γ、TNF-α或IL-12的中和作用显著降低了IL-10（-/-）脾细胞中考克斯-2的诱导，表明炎性细胞因子产生的增加介导了IL-10（-/-）小鼠中考克斯-2的诱导。用低剂量LPS处理IL-10（-/-）小鼠导致脾脏中考克斯-2 mRNA的显著诱导，而野生型小鼠具有最小的考克斯-2 mRNA表达。这些发现表明，除了IL-10在调节炎性细胞因子中的中心作用之外，内源性IL-10是响应于LPS的PG产生的重要调节剂，
IL-IO is a potent anti-inflammatory and immune regulatory cytokine, IL-10(-/-) mice produce exaggerated amounts of inflammatory cytokines when stimulated with LPS, indicating that endogenous IL-10 is a central regulator of inflammatory cytokine production in vivo. PGs are lipid mediators that are also produced in large amounts during the inflammatory response. To study the role of IL-10 in the regulation of PG production during the acute inflammatory response, we evaluated LPS-induced cyclooxygenase (COX) expression and PC production in wild-type (wt) and IL-10(-/-) mice. LPS induced PGE, production from IL-10(-/-) spleen cells was 5.6-fold greater than that from wt spleen cells. LPS stimulation resulted in the induction of COX-2 mRNA and protein in both wt and IL-10(-/-) spleen cells; however, the magnitude of increase in COX-2 mRNA was 5.5-fold greater in IL-10(-/-) mice as compared with wt mice. COX-I protein levels mere not affected by LPS stimulation in either wt or IL-10-/mice. Neutralization of IFN-gamma, TNF-alpha or IL-12 markedly decreased the induction of COX-2 in IL-10(-/-) spleen cells, suggesting that increased inflammatory cytokine production mediates much of the COX-2 induction in IL-10(-/-) mice. Treatment of IL-10(-/-) mice with low doses of LPS resulted in a marked induction of COX-2 mRNA in the spleen, whereas wt mice had minimal expression of COX-2 mRNA, These findings indicate that, in addition to IL-10's central role in the regulation of inflammatory cytokines, endogenous IL-10 is an important regulator of PG production in the response to LPS,