Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of America.
PLoS One. 2013 Aug 2;8(8):e72772. doi: 10.1371/journal.pone.0072772. Print 2013.
BACKGROUND/OBJECTIVE: Phosphatidylserine (PS) exposed on apoptotic cells has been shown to stimulate production of transforming growth factor-β (TGF-β) and promote anti-inflammatory responses. However, the PS receptor(s) responsible for this induction has not been clearly determined.
METHODOLOGY/PRINCIPAL FINDINGS: In the present study, using RAWTβRII cells in which a truncated dominant negative TGF-β receptor II was stably transfected in order to avoid auto-feedback induction of TGF-β, we show that TGF-β1 synthesis is initiated via activation of the scavenger receptor, CD36. The response requires exposure of PS on the apoptotic cell surface and was absent in macrophages lacking CD36. Direct activation of CD36 with an anti-CD36 antibody initiated TGF-β1 production, and signaling pathways involving both Lyn kinase and ERK1/2 were shown to participate in CD36-driven TGF-β1 expression.
CONCLUSION/SIGNIFICANCE: Since CD36 has been previously implicated in activation of secreted latent TGF-β, the present study indicates its role in the multiple steps to generation of this important biological mediator.
背景/目的：凋亡细胞表面暴露的磷脂酰丝氨酸（PS）已被证明能刺激转化生长因子-β（TGF-β）的产生，并促进抗炎反应。然而，负责这种诱导的 PS 受体（s）尚未明确确定。
方法/主要发现：在本研究中，我们使用 RAWTβRII 细胞，该细胞中稳定转染了截断的显性负 TGF-β受体 II，以避免 TGF-β的自动反馈诱导，表明 TGF-β1 的合成是通过清道夫受体 CD36 的激活而启动的。该反应需要凋亡细胞表面 PS 的暴露，而在缺乏 CD36 的巨噬细胞中则不存在。用抗 CD36 抗体直接激活 CD36 会引发 TGF-β1 的产生，并且涉及 Lyn 激酶和 ERK1/2 的信号通路被证明参与了 CD36 驱动的 TGF-β1 表达。
结论/意义：由于 CD36 先前已被牵涉到分泌潜伏 TGF-β的激活中，本研究表明其在生成这种重要生物介质的多个步骤中发挥作用。
