Monteleone G, Parrello T, Monteleone I, Tammaro S, Luzza F, Pallone F
Dipartimento di Medicina Sperimentale e Clinica 'G. Salvatore', Università di Catanzaro, Magna Graecia, Catanzaro, Italy.
Clin Exp Immunol. 1999 Sep;117(3):469-75. doi: 10.1046/j.1365-2249.1999.00991.x.
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-gamma and PGE2 on lipopolysaccharide (LPS)-stimulated LPMC IL-12 production. Normal LPMC cultures were run in the presence or absence of IFN-gamma 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-gamma facilitated LPS-stimulated IL-12, whereas it completely abrogated IL-10 production. IL-12 release by LPMC stimulated with IFN-gamma and LPS was significantly inhibited by exogenous IL-10. The addition of PGE2 to IFN-gamma-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-gamma and PGE2 modulate differently the LPMC responsiveness to LPS in terms of IL-12 synthesis.
白细胞介素-12在慢性结肠炎期间调节Th1免疫反应。人类肠道中调节白细胞介素-12合成的机制尚不清楚。本研究的目的是探讨干扰素-γ和前列腺素E2对脂多糖（LPS）刺激的淋巴细胞性脉络丛脑膜炎细胞（LPMC）白细胞介素-12产生的影响。在LPS刺激之前，正常的LPMC培养物在有或没有干扰素-γ和/或前列腺素E2的情况下进行培养。为了研究内源性前列腺素E2对LPS刺激的白细胞介素-12释放的作用，在LPS刺激之前向LPMC培养物中加入消炎痛。通过酶联免疫吸附测定法（ELISA）测量白细胞介素-12、白细胞介素-10和白细胞介素-8。在未刺激的或LPS刺激的LPMC培养物中均未检测到白细胞介素-12。相反，LPMC对LPS作出反应释放白细胞介素-8（650±125皮克/毫升）和白细胞介素-10（75±25皮克/毫升）。用干扰素-γ处理LPMC促进了LPS刺激的白细胞介素-12产生，而它完全消除了白细胞介素-10的产生。干扰素-γ和LPS刺激的LPMC释放的白细胞介素-12被外源性白细胞介素-10显著抑制。向用干扰素-γ处理的LPMC培养物中加入前列腺素E2以剂量依赖的方式抑制LPS诱导的白细胞介素-12分泌。此外，在用消炎痛和LPS处理的LPMC培养物的上清液中可检测到白细胞介素-12（85±25皮克/毫升）。与对白细胞介素-12的作用相反，前列腺素E2显著增强LPS刺激的LPMC白细胞介素-10产生。然而，前列腺素E2对白细胞介素-12的抑制仅被抗白细胞介素-10部分逆转。在一个简化的LPS耐受模型中，我们最终表明单核细胞衍生的巨噬细胞在重复LPS刺激后白细胞介素-12产生减少。在这些细胞培养物中，消炎痛消除了LPS脱敏的诱导。就白细胞介素-12合成而言，干扰素-γ和前列腺素E2对LPMC对LPS的反应性有不同的调节作用。
