Pirhonen Jaana, Matikainen Sampsa, Julkunen Ilkka
Department of Microbiology, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland.
J Immunol. 2002 Nov 15;169(10):5673-8. doi: 10.4049/jimmunol.169.10.5673.
IL-23 is a novel cytokine that promotes the proliferation of naive and memory T cells and stimulates their IFN-gamma production. Besides functional similarities, IL-23 bears structural resemblance to IL-12. Biologically active IL-23 is a heterodimer whose p40 subunit is identical to IL-12p40 while its p19 subunit is distantly related to IL-12p35. In the present study we demonstrate that human monocyte-derived macrophages are able to produce IL-23 in response to virus infection. Sendai virus stimulates the expression of p19 and p40 mRNAs in macrophages. Furthermore, it enhances p35 mRNA expression and the production of IL-12. Influenza A virus, in contrast, fails to stimulate IL-12 or IL-23 expression in macrophages. IL-12 and IL-23 contribute to the IFN-gamma-inducing activity that cell culture supernatant from Sendai virus-infected macrophages show in NK-92 cells. The induction of IFN-gamma production occurs in concert with IFN-alphabeta and IL-18, which are also secreted from the virus-infected cells. The IFN-gamma-inducing activity is inhibited by IL-4, which down-regulates the transcription of p19 and p40 genes and the secretion of IFN-alphabeta, IL-12, and IL-18. IFN-gamma, in contrast, up-regulates the p19 and p40 mRNA expression in Sendai virus infection. Thus, IL-4 and IFN-gamma serve as opposing factors in the regulation of IFN-gamma-inducing cytokines, including IL-23, in macrophages.
白细胞介素-23(IL-23)是一种新型细胞因子,可促进初始T细胞和记忆T细胞的增殖,并刺激它们产生γ干扰素(IFN-γ)。除了功能相似外,IL-23在结构上与IL-12也有相似之处。具有生物活性的IL-23是一种异二聚体,其p40亚基与IL-12p40相同,而其p19亚基与IL-12p35的关系较远。在本研究中,我们证明人单核细胞衍生的巨噬细胞能够在病毒感染时产生IL-23。仙台病毒刺激巨噬细胞中p19和p40 mRNA的表达。此外,它还增强p