Inhibitory mechanism of Interferon-γ production of peripheral blood mononuclear cells stimulated with OK-432 by soluble factor derived from oral cancer cells

通过添加健康志愿者的条件培养液(CM)，建立了口腔癌患者免疫状态的体内模拟模型。OK-432刺激的PBMC产生大量的干扰素-γ，而CM对OK-432诱导的PBMC产生的干扰素-γ和细胞毒活性均有抑制作用。为了检测这些对干扰素-γ产生的抑制作用，抑制细胞因子的中和不能恢复CM诱导的干扰素-γ的产生，提示未知的细胞因子与干扰素-γ的产生抑制有关。CMS中的某些可溶性因子通过抑制γ的表达抑制IL-12的产生，从而抑制PBMC产生干扰素。

An in vivo simulation model was established of the immune status of patients with oral cancer by adding conditioned media (CM) derived from a healthy volunteer. PBMCs stimulated with OK-432 produced a large amount of IFN-γ ; however, both IFN-γ production and cytotoxic activity of PBMCs induced by OK-432 were inhibited by the addiction of CM. In order to examine these inhibitory effects against IFN-γ production, neutralization of inhibitory cytokines did not recover IFN-γ production induced by CM, suggesting the relation of unknown cytokines from the inhibition of IFN-γ production.Thus, the genes that regulated IFN-γ production were retrieved using cDNA microarray analysis. Some soluble factors included in CMs inhibited IFN-γ production in PBMCs by the suppression of IL-12 production via the inhibition of CD40 expression.