Wittmann M, Zwirner J, Larsson V A, Kirchhoff K, Begemann G, Kapp A, Götze O, Werfel T
Department of Dermatology and Allergology, Hannover Medical University, Germany.
J Immunol. 1999 Jun 1;162(11):6763-9.
IL-12 is a key mediator of the immune response, skewing T lymphocytes toward a type 1 cytokine pattern. Priming with IFN-gamma or GM-CSF is required for expression of IL-12p70 by cells in which IL-12 is inducible by bacterial products such as LPS. We here show for the first time that the production of bioactive IL-12 by human monocytes can be significantly suppressed by C5a if applied to IFN-gamma-primed monocytes before LPS stimulation. There was a dose-dependent suppression by IL-12 (p70) on the levels of intracellular cytokine production and cytokine secretion. mRNA studies consistently showed a reduction of IL-12p40 and IL-12p35 expression by stimulation in the presence of C5a. The results of several different experimental approaches suggest that IL-12 down-regulation was not due to endogenous IL-10, IL-4, or PGE2 production induced by C5a. Moreover, stimulation of IFN-gamma-primed monocytes with C5a did not lead to a down-regulation of the CD14 Ag, which is an LPS receptor. These findings show that the anaphylatoxin C5a has the capacity to directly interact with the complex regulation of IL-12.
白细胞介素-12是免疫反应的关键介质，使T淋巴细胞倾向于1型细胞因子模式。对于可被细菌产物如脂多糖诱导产生白细胞介素-12的细胞，需要用γ干扰素或粒细胞-巨噬细胞集落刺激因子进行预处理才能表达白细胞介素-12p70。我们首次在此表明，如果在脂多糖刺激前将C5a应用于经γ干扰素预处理的单核细胞，人单核细胞产生的生物活性白细胞介素-12可被显著抑制。白细胞介素-12（p70）对细胞内细胞因子产生水平和细胞因子分泌存在剂量依赖性抑制。mRNA研究一致表明，在C5a存在的情况下进行刺激会使白细胞介素-12p40和白细胞介素-12p35表达减少。几种不同实验方法的结果表明，白细胞介素-12的下调并非由于C5a诱导产生内源性白细胞介素-10、白细胞介素-4或前列腺素E2。此外，用C5a刺激经γ干扰素预处理的单核细胞不会导致作为脂多糖受体的CD14抗原下调。这些发现表明过敏毒素C5a有能力直接参与白细胞介素-12的复杂调节。
