Interferon‐gamma (IFN‐γ) and prostaglandin E2 (PGE2) regulate differently IL‐12 production in human intestinal lamina propria mononuclear cells (LPMC)

Interferon‐gamma (IFN‐γ) and prostaglandin E2 (PGE2) regulate differently IL‐12 production in human intestinal lamina propria mononuclear cells (LPMC)
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干扰素-γ (IFN-γ) 和前列腺素 E2 (PGE2) 在人肠固有层单核细胞 (LPMC) 中以不同方式调节 IL-12 的产生

DOI:
10.1046/j.1365-2249.1999.00991.x
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发表时间:
1999
影响因子:
4.6
通讯作者:
Francesco Pallone
Francesco Pallone
中科院分区:
医学3区
文献类型:
--
作者:
G. Monteleone;T. Parrello;I. Monteleone;S. Tammaro;Francesco Luzza;Francesco Pallone

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IL-12 在慢性结肠炎期间调节 Th1 免疫反应。人们对调节人肠道 IL-12 合成的机制知之甚少。本研究的目的是研究 IFN-γ 和 PGE2 对脂多糖 (LPS) 刺激的 LPMC IL-12 产生的影响。在 LPS 刺激之前,在存在或不存在 IFN-γ 和/或 PGE2 的情况下运行正常 LPMC 培养物。为了检查内源性 PGE2 对 LPS 刺激的 IL-12 释放的作用,在 LPS 刺激之前向 LPMC 培养物中添加吲哚美辛。通过ELISA测定IL-12、IL-10和IL-8。在未刺激或 LPS 刺激的 LPMC 培养物中均未检测到 IL-12。相反,LPMC 响应 LPS 释放 IL-8 (650±125pg/ml) 和 IL-10 (75±25pg/ml)。用 IFN-γ 处理 LPMC 促进了 LPS 刺激的 IL-12,而完全消除了 IL-10 的产生。外源性 IL-10 显着抑制 IFN-γ 和 LPS 刺激的 LPMC 释放 IL-12。在 IFN-γ 处理的 LPMC 培养物中添加 PGE2 以剂量依赖性方式抑制 LPS 诱导的 IL-12 分泌。此外,在用吲哚美辛和 LPS 处理的 LPMC 培养物上清液中可检测到 IL-12(85±25pg/ml)。与对 IL-12 的影响相反,PGE2 显着增强了 LPS 刺激的 LPMC IL-10 的产生。然而,PGE2 对 IL-12 的抑制作用只能被抗 IL-10 部分逆转。在 LPS 耐受的简化模型中,我们最终证明单核细胞来源的巨噬细胞在重复 LPS 刺激后表现出 IL-12 产生减少。在这些细胞培养物中,吲哚美辛消除了 LPS 脱敏的诱导。 IFN-γ 和 PGE2 在 IL-12 合成方面不同地调节 LPMC 对 LPS 的反应。
IL‐12 modulates Th1 immune response during chronic colitis. Mechanisms regulating IL‐12 synthesis in human intestine are poorly understood. The aim of this study was to investigate the effect of IFN‐γ and PGE2 on lipopolysaccharide (LPS)‐stimulated LPMC IL‐12 production. Normal LPMC cultures were run in the presence or absence of IFN‐γ and/or PGE2 before LPS stimulation. To examine the role of endogenous PGE2 on LPS‐stimulated IL‐12 release, LPMC cultures were added of indomethacin before LPS stimulation. IL‐12, IL‐10 and IL‐8 were measured by ELISA. No IL‐12 was detected in either unstimulated or LPS‐stimulated LPMC cultures. In contrast, LPMC released IL‐8 (650 ± 125 pg/ml) and IL‐10 (75 ± 25 pg/ml) in response to LPS. Treatment of LPMC with IFN‐γ facilitated LPS‐stimulated IL‐12, whereas it completely abrogated IL‐10 production. IL‐12 release by LPMC stimulated with IFN‐γ and LPS was significantly inhibited by exogenous IL‐10. The addition of PGE2 to IFN‐γ‐treated LPMC cultures inhibited in a dose‐dependent manner LPS‐induced IL‐12 secretion. Furthermore, IL‐12 was detectable (85 ± 25 pg/ml) in the supernatants of LPMC cultures treated with indomethacin and LPS. In contrast to the effect on IL‐12, PGE2 significantly augmented LPS‐stimulated LPMC IL‐10 production. However, the inhibition of IL‐12 by PGE2 was only partially reversed by anti‐IL‐10. In a simplified model of LPS tolerance, we finally showed that monocyte‐derived macrophages exhibited reduced IL‐12 production after repeat LPS stimulation. In these cell cultures, indomethacin abrogated the induction of LPS desensitization. IFN‐γ and PGE2 modulate differently the LPMC responsiveness to LPS in terms of IL‐12 synthesis.
DOI: 10.1172/jci113938
发表时间: 1989-02-01
影响因子: 15.9
作者:
MADARA, JL;STAFFORD, J
通讯作者: STAFFORD, J
DOI: --
发表时间: 1993
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Adams,RB;Planchon,SM;Roche,JK
通讯作者: Roche,JK
DOI: 10.1016/0167-5699(91)90064-z
发表时间: 1991-10-01
期刊: IMMUNOLOGY TODAY
影响因子: --
作者:
PHIPPS, RP;STEIN, SH;ROPER, RL
通讯作者: ROPER, RL