Leal-Berumen I, O'Byrne P, Gupta A, Richards C D, Marshall J S
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
J Immunol. 1995 May 1;154(9):4759-67.
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.
肥大细胞传统上与涉及组胺等介质短期释放的急性反应相关。我们之前已经表明，肥大细胞可以在不预先释放组胺的情况下产生白细胞介素-6（IL-6）。在本研究中，我们检验了肥大细胞IL-6产生可被前列腺素（PGs）选择性调节的假说。将高度纯化的大鼠腹膜肥大细胞单独在前列腺素E1（PGE1）、前列腺素E2（PGE2）或前列腺素D2（PGD2）存在的情况下培养，或与抗免疫球蛋白E（anti-IgE）或细菌脂多糖（LPS）联合培养。10分钟后评估组胺释放；18小时后测量上清液中IL-6和肿瘤坏死因子-α（TNF-α）的产生。PGE1和PGE2诱导肥大细胞产生IL-6的水平与抗IgE激活的细胞中观察到的水平相似。相比之下，PGE1和PGE2抑制TNF-α的组成性产生，但PGD2无此作用。PGE2具有协同作用，在LPS存在时诱导IL-6产生，而在抗IgE存在时观察到相加作用。在10分钟时间点，单独的前列腺素均未诱导显著的组胺释放。然而，PGE2与抗IgE同时添加时显著增加组胺释放。在抗IgE或LPS激活的情况下，氟比洛芬不改变肥大细胞IL-6或TNF-α的产生。皮质类固醇地塞米松显著抑制对每种刺激的IL-6产生。这些关于肥大细胞细胞因子产生选择性调节的观察结果对于理解在涉及前列腺素合成的炎症过程中肥大细胞与其他细胞相互作用的机制很重要。
