响应凋亡细胞时TGF-β产生的转录和翻译调控。
Transcriptional and translational regulation of TGF-beta production in response to apoptotic cells.
作者信息
Xiao Yi Qun, Freire-de-Lima Celio G, Schiemann William P, Bratton Donna L, Vandivier R William, Henson Peter M
机构信息
Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
出版信息
J Immunol. 2008 Sep 1;181(5):3575-85. doi: 10.4049/jimmunol.181.5.3575.
Interaction between apoptotic cells and phagocytes through phosphatidylserine recognition structures results in the production of TGF-beta, which has been shown to play pivotal roles in the anti-inflammatory and anti-immunogenic responses to apoptotic cell clearance. Using 3T3-TbetaRII and RAWTbetaRII cells in which a truncated dominant-negative TGF-beta receptor II was stably transfected to avoid autofeedback induction of TGF-beta, we investigate the mechanisms by which TGF-beta was produced through PSRS engagement. We show, in the present study, that TGF-beta was regulated at both transcriptional and translational steps. P38 MAPK, ERK, and JNK were involved in TGF-beta transcription, whereas translation required activation of Rho GTPase, PI3K, Akt, and mammalian target of rapamycin with subsequent phosphorylation of translation initiation factor eukaryotic initiation factor 4E. Strikingly, these induction pathways for TGF-beta production were different from those initiated in the same cells responding to LPS or PMA.
凋亡细胞与吞噬细胞通过磷脂酰丝氨酸识别结构相互作用，导致转化生长因子-β（TGF-β）的产生，TGF-β已被证明在对凋亡细胞清除的抗炎和抗免疫原性反应中起关键作用。利用稳定转染截短的显性负性TGF-β受体II的3T3-TβRII和RAW TβRII细胞，以避免TGF-β的自反馈诱导，我们研究了通过磷脂酰丝氨酸识别结构（PSRS）参与产生TGF-β的机制。在本研究中，我们表明TGF-β在转录和翻译步骤均受到调控。P38丝裂原活化蛋白激酶（MAPK）、细胞外信号调节激酶（ERK）和c-Jun氨基末端激酶（JNK）参与TGF-β转录，而翻译则需要激活Rho鸟苷三磷酸酶（GTPase）、磷脂酰肌醇-3激酶（PI3K）、蛋白激酶B（Akt）和雷帕霉素靶蛋白（mTOR），随后翻译起始因子真核起始因子4E（eIF4E）发生磷酸化。值得注意的是，这些TGF-β产生的诱导途径与在同一细胞中对脂多糖（LPS）或佛波酯（PMA）作出反应时启动的途径不同。
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