Prostaglandin E2 is a major soluble factor produced by stromal cells for preventing inflammatory cytokine production from dendritic cells
Prostaglandin E2 is a major soluble factor produced by stromal cells for preventing inflammatory cytokine production from dendritic cells
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DOI：
10.1093/intimm/dxn078
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发表时间：
2008-09-01
影响因子：
4.4
通讯作者：
Yoshimura, Akihiko
中科院分区：
文献类型：
--
作者：
Shiraishi, Hiroshi;Yoshida, Hideyuki;Yoshimura, Akihiko
树突状细胞(DC)是一种特殊的抗原提呈细胞，在启动免疫反应中起着关键作用。然而，DC的成熟通常受到基质微环境的强烈限制，特别是在非淋巴组织中，如皮肤和粘膜。尽管基质细胞对DC成熟的抑制作用已有文献记载，但这种抑制作用的分子基础尚未建立。在这项研究中，我们研究了成纤维细胞在DC体外成熟中的作用。小鼠胚胎成纤维细胞(MEF)强烈抑制内毒素诱导的DC成熟。虽然抑制II类MHC和CD40需要DC-MEF接触，但MEF培养上清液中的可溶性因子足以抑制IL-12和肿瘤坏死因子-a的产生。通过分子大小选择和高效液相分析，我们确定前列腺素E-2(PGE(2))是MEF分泌的一种主要的可溶性抑制因子。环氧合酶抑制剂抑制MEF产生抑制因子的事实证实了这一点。这些结果表明，PGE2是MEFS产生的抑制DC产生炎性细胞因子的主要可溶性因子，而MEFS和DC之间需要一种接触机制来抑制诱导T细胞刺激分子的产生。
Dendritic cells (DCs) are specialized antigen-presenting cells that play pivotal roles in initiating immune responses. However, DC maturation is usually strongly restricted by the stromal microenvironment, especially in non-lymphoid tissues, such as skin and mucosa. Although suppression of DC maturation by stromal cells has been well documented, the molecular basis of this suppression has not been established. In this study, we examined the role of fibroblasts for DC maturation in vitro. The mouse embryonic fibroblasts (MEFs) strongly suppressed LPS-induced DC maturation. Although suppression of class II MHC and CD40 required DC-MEF contact, soluble factors in the culture supernatant of MEFs were sufficient for the suppression of IL-12 and tumor necrosis factor-a production. Using molecular-size selection and HPLC, we determined that prostaglandin E-2 (PGE(2)) is a major soluble inhibitory factor secreted by MEFs. This was confirmed by the fact that cyclooxygenase inhibitors inhibited the production of the suppressive factor by MEFs. These results suggest that PGE2 is a major soluble factor produced by MEFs for the suppression of inflammatory cytokine production from DCs, while a contact mechanism between MEFs and DCs is required for the suppression to induce T cell-stimulating molecules.