Prostanoid enhancement of interleukin-6 production by rat peritoneal mast cells.
Prostanoid enhancement of interleukin-6 production by rat peritoneal mast cells.
复制标题
前列腺素增强大鼠腹膜肥大细胞产生白细胞介素 6。
作者：
I. Leal;P. O'Byrne;A. Gupta;C. Richards;J. Marshall
肥大细胞传统上与急性反应有关，涉及介质如组胺的短期释放。我们以前已经表明，肥大细胞可以产生IL-6，而无需事先释放组胺。在这项研究中，我们检查的假设，肥大细胞IL-6的生产可以选择性地调节前列腺素。高度纯化的大鼠腹腔肥大细胞培养在PGE 1，PGE 2，或PGD 2单独或与抗IgE或细菌LPS组合的存在下。10分钟后评估组胺释放; 18小时后测量上清液中IL-6和TNF-α的产生。肥大细胞IL-6的产生诱导PGE 1和PGE 2的抗IgE激活的细胞中观察到的类似的水平。相反，TNF-α的组成性产生被PGE 1和PGE 2抑制，但不被PGD 2抑制。PGE 2具有协同效应，在LPS存在下诱导IL-6，而在抗IgE存在下观察到累加效应。在10分钟时间点，单独的前列腺素类均未诱导显著的组胺释放。然而，当与抗IgE同时加入时，PGE 2显著增加组胺释放。氟比洛芬在抗IgE或LPS激活的情况下不改变肥大细胞IL-6或TNF-α的产生。皮质类固醇地塞米松显著抑制了IL-6的产生。肥大细胞细胞因子产生的选择性调节的这些观察对于理解肥大细胞在涉及前列腺素类合成的炎症过程中与其他细胞相互作用的机制是重要的。
Mast cells are traditionally associated with an acute response involving the short-term release of mediators such as histamine. We have shown previously that mast cells can produce IL-6 without prior histamine release. In this study we examined the hypothesis that mast cell IL-6 production can be selectively regulated by PGs. Highly purified rat peritoneal mast cells were cultured in the presence of PGE1, PGE2, or PGD2 alone or in combination with anti-IgE or bacterial LPS. Histamine release was assessed after 10 min; IL-6 and TNF-alpha production was measured in supernatants after 18 h. Mast cell IL-6 production was induced by PGE1 and PGE2 to a similar level to that observed in anti-IgE-activated cells. In contrast, constitutive production of TNF-alpha was inhibited by PGE1 and PGE2, but not by PGD2. PGE2 had a synergistic effect, inducing IL-6 in the presence of LPS, whereas an additive effect was observed in the presence of anti-IgE. None of the prostanoids alone induced significant histamine release at the 10-min time point. However, PGE2 significantly increased histamine release when added concurrently with anti-IgE. Flurbiprofen in the context of anti-IgE or LPS activation did not alter mast cell IL-6 or TNF-alpha production. IL-6 production in response to each of the stimuli was significantly inhibited by the corticosteroid dexamethasone. These observations of selective modulation of mast cell cytokine production are important to understand the mechanisms by which mast cells interact with other cells during an inflammatory process involving prostanoid synthesis.