Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Valladolid, Spain.
Mol Immunol. 2011 Oct;49(1-2):97-106. doi: 10.1016/j.molimm.2011.07.022. Epub 2011 Aug 26.
Contact of apoptotic cells (AC) with phagocytes tilts the balance of pro-inflammatory and anti-inflammatory cytokines. To address the cell- and stimulus-dependency of this mechanism, human monocyte-derived dendritic cells were treated with Jurkat AC in the presence and absence of different stimuli. AC reduced the production of IL-23 and enhanced the production of IL-10 elicited by zymosan, but they did not influence IL-12 p70 production nor did they modify the effect of LPS. Since formation of lipid bodies (LB) and PGE(2) production have been associated with IL-10 induction, the effect of PGE(2), the formation of LB, and the role of PPAR-γ were assessed. Exogenous PGE(2) enhanced IL-10 expression, but no evidence of PGE(2) production elicited by AC was obtained. Inhibition of PPAR-γ activity reduced the production of IL-10 both in the presence and in the absence of AC, but formation of LB in response to zymosan and AC was not observed. Notably, AC induced a transient nuclear translocation of both the CREB coactivator CRTC2/TORC2 and the homeodomain protein PBX1, which are involved in the CREB/HOX/PBX/MEIS transcription complex. These data show a selective effect of AC on the production of cytokines elicited by the fungal surrogate zymosan through the enhancement of CREB-dependent transcription.
凋亡细胞（AC）与吞噬细胞的接触会改变促炎和抗炎细胞因子的平衡。为了研究这种机制的细胞和刺激依赖性，我们用人单核细胞来源的树突状细胞在存在和不存在不同刺激物的情况下用 Jurkat AC 处理。AC 减少了几丁质诱导的 IL-23 的产生并增强了 IL-10 的产生，但它们不影响 IL-12 p70 的产生，也不改变 LPS 的作用。由于脂滴（LB）的形成和 PGE（2）的产生与 IL-10 的诱导有关，因此评估了 PGE（2）的作用、LB 的形成以及 PPAR-γ 的作用。外源性 PGE（2）增强了 IL-10 的表达，但没有发现 AC 诱导的 PGE（2）产生的证据。PPAR-γ 活性的抑制减少了 IL-10 的产生，无论是在存在 AC 的情况下还是在不存在 AC 的情况下，但没有观察到对几丁质和 AC 的 LB 形成。值得注意的是，AC 诱导了 CREB 共激活因子 CRTC2/TORC2 和同源域蛋白 PBX1 的瞬时核易位，这两种蛋白都参与了 CREB/HOX/PBX/MEIS 转录复合物。这些数据表明，AC 对真菌替代物几丁质诱导的细胞因子产生具有选择性影响，通过增强 CREB 依赖性转录。
