HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Xiao, Y. Q. Articles by Henson, P. M. Search for Related Content PubMed PubMed Citation Articles by Xiao, Y. Q. Articles by Henson, P. M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH

Transcriptional and Translational Regulation of TGF-β Production in Response to Apoptotic Cells¹

Yi Qun Xiao^*, Celio G. Freire-de-Lima^*,, William P. Schiemann, Donna L. Bratton^*, R. William Vandivier and Peter M. Henson^2,*

^* Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206; Instituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; and Division of Pulmonary Sciences and Critical Care Medicine and Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045

Interaction between apoptotic cells and phagocytes through phosphatidylserine recognition structures results in the production of TGF-β, which has been shown to play pivotal roles in the anti-inflammatory and anti-immunogenic responses to apoptotic cell clearance. Using 3T3-TβRII and RAWTβRII cells in which a truncated dominant-negative TGF-β receptor II was stably transfected to avoid autofeedback induction of TGF-β, we investigate the mechanisms by which TGF-β was produced through PSRS engagement. We show, in the present study, that TGF-β was regulated at both transcriptional and translational steps. P38 MAPK, ERK, and JNK were involved in TGF-β 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-β production were different from those initiated in the same cells responding to LPS or PMA.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants HL81151, GM61031, AI058228, and HL34303. C.G.F.-d.-L. is recipient of Long-Term Fellowship LT-00606-2002 from Human Frontier Science Program.

² Address correspondence and reprint requests to Dr. Peter M. Henson, Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail address: hensonp{at}njc.org

³ Abbreviations used in this paper: PS, phosphatidylserine; 4EBP-1, 4E-binding protein-1; eIF4E, eukaryotic initiation factor 4E; mTOR, mammalian target of rapamycin; PSRS, PS recognition structure; SBE, Smad-binding elements.