IL-6 and IL-8 production from cultured human endothelial cells stimulated by infection with Rickettsia conorii via a cell-associated IL-1 alpha-dependent pathway
IL-6 and IL-8 production from cultured human endothelial cells stimulated by infection with Rickettsia conorii via a cell-associated IL-1 alpha-dependent pathway
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DOI：
10.1172/jci118354
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发表时间：
1995-12-01
影响因子：
15.9
通讯作者：
Bongrand, P
中科院分区：
文献类型：
--
作者：
Kaplanski, G;Teysseire, N;Bongrand, P
地中海斑疹热是由康氏立克次体感染引起的，其特征是全身性血管炎。这种血管炎被认为是由于由R.科诺里。然而，内皮细胞上细胞因子的产生和活性是炎症反应的重要途径，也是血管炎发生的重要机制之一。Conorii主动分泌高水平的IL-8和IL-6（与未感染的细胞相比，分别为P < 0.002和P < 0.03）。在培养上清液中未检测到IL-1 α、IL-1 β或TNF α。然而，IL-6和IL-8的产生在很大程度上是由于在R上表达的IL-1 α的细胞相关形式。由于加入IL-1受体拮抗剂或抗IL-1 α抗体（分别为60%抑制，P <0.01和65%抑制，P <0.05），这些细胞因子的产生被抑制了80%（P = 0.0001）和85%（P <0.04），并且在R.而未感染的HUVEC则无明显变化（P> 0.01）。立克次体脂多糖似乎不参与其中，因为多粘菌素B并不减少细胞因子的分泌。相反，胞内R. conorii似乎是诱导IL-1 α和随后的IL-8所必需的，因为福尔马林固定的R. conorii不诱导细胞因子的产生。Conori感染的HUVEC通过诱导细胞相关的IL-1 α分泌IL-6和IL-8，为地中海斑点热中观察到的血管炎提供了可能的机制。
Mediterranean spotted fever due to infection by Rickettsia conorii, is characterized by a general vasculitis. This vasculitis is thought to be due to a direct injury to endothelial cells induced by R. conorii. However, production and activity of cytokines on endothelial cells is an important pathway in inflammation, and part of the underlying mechanism of vasculitis, In the present studies, human umbilical vein endothelial cells (HUVEC) infected with R. conorii actively secrete high levels of IL-8 and IL-6 (P < 0.002, and P < 0.03, respectively, compared with uninfected cells). IL-1 alpha, IL-1 beta, or TNF alpha were not detected in the culture supernates. Nevertheless, IL-6 and IL-8 production was due, in a large part, to a cell-associated form of IL-1 alpha expressed on R. conorii-infected HUVEC, since production of these cytokines was suppressed by 80% (P = 0.0001) and 85% (P < 0.04) by the addition of IL-1 receptor antagonist, or anti-IL-1 alpha antibodies (60% inhibition, P < 0.01 and 65% inhibition, P < 0.05, respectively) and IL-1 alpha was measured after lysis of R. conorii-infected HUVEC but not in uninfected cells (P < 0.01). Rickettsial lipopolysaccharide does not seem to be involved, since polymyxin B did not reduce cytokine secretion. On the contrary, infection by intracellular R. conorii appears to be necessary to induce IL-1 alpha and subsequently IL-8, since formalin-fixed R. conorii did not induce cytokine production, These observations demonstrate that R. conorii-infected HUVEC secrete IL-6 and IL-8 via the induction of cell-associated IL-1 alpha, providing a possible mechanism for the vasculitis observed in Mediterranean spotted fever.