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PMID: 18714031 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Transcriptional and translational regulation of TGF-beta production in response to apoptotic cells.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 181 ·No. 5 ·2008-09-01 ·Pages 3575-85

Xiao YQ, Freire-de-Lima CG, Schiemann WP, Bratton DL, Vandivier RW, Henson PM

Abstract

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.

MeSH Terms
3T3 Cells Animals Apoptosis Cell Line Fibroblasts/immunology,metabolism Gene Expression Regulation/immunology Macrophages/immunology,metabolism Mice Phosphatidylserines/metabolism Protein Biosynthesis Signal Transduction Transcription, Genetic Transforming Growth Factor beta/biosynthesis
Chemicals
Phosphatidylserines Transforming Growth Factor beta
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Xiao Yi Qun
Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Freire-de-Lima Celio G
Schiemann William P
Bratton Donna L
Vandivier R William
Henson Peter M
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
1550-6606
DOI
10.4049/jimmunol.181.5.3575
Published
2008-09-01
Pages
3575-85
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC2583327
Subset
IM
Grants
NHLBI NIH HHS · P01 HL034303-20 · United States
NIAID NIH HHS · R01 AI058228 · United States
NIAID NIH HHS · R01 AI058228-04 · United States
NHLBI NIH HHS · HL34303 · United States
NHLBI NIH HHS · R01 HL068864 · United States
NIAID NIH HHS · R56 AI058228 · United States
NIGMS NIH HHS · R01 GM061031-07 · United States
NHLBI NIH HHS · R01 HL081151-04 · United States
NIGMS NIH HHS · GM61031 · United States
NHLBI NIH HHS · HL81151 · United States
NHLBI NIH HHS · R01 HL081151 · United States
NHLBI NIH HHS · P01 HL034303 · United States
NIGMS NIH HHS · R01 GM061031 · United States
NIAID NIH HHS · AI058228 · United States
External Links
PubMed source DOI: 10.4049/jimmunol.181.5.3575 PMC Full Text View journal details
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