Transcriptional and translational regulation of TGF-beta production in response to apoptotic cells.
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.
Xiao
Yi Qun
YQ
Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Freire-de-Lima
Celio G
CG
Schiemann
William P
WP
Bratton
Donna L
DL
Vandivier
R William
RW
Henson
Peter M
PM
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010718:Phosphatidylserines / Q000378:metabolism; D014176:Protein Biosynthesis; D015398:Signal Transduction; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D010718:Phosphatidylserines; D016212:Transforming Growth Factor beta