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 Zhao, W. Articles by Schwartz, L. B. Search for Related Content PubMed PubMed Citation Articles by Zhao, W. Articles by Schwartz, L. B. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Genetics Home Reference

TGF-β1 Attenuates Mediator Release and De Novo Kit Expression by Human Skin Mast Cells through a Smad-Dependent Pathway¹

Wei Zhao^*, Gregorio Gomez, Shao-Hua Yu^*, John J. Ryan and Lawrence B. Schwartz^2,

^* Department of Pediatrics and Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298; and Department of Biology, Virginia Commonwealth University, Richmond, VA 23284

TGF-β has pleiotropic effects on many cell types at different stages of their development, including mast cells. The present study examines the effects of TGF-β on human skin mast cells of the MC_TC type. The expression of TGF-β receptors (TGF-R) was verified at the mRNA and protein levels for TGF-RI and TGF-RII, and at the mRNA level for accessory molecules β-glycan and endoglin. TGF-β did not affect mast cell viability after 1 wk at concentrations 10 ng/ml, but at 50 ng/ml caused significant cell death. TGF-β inhibited surface and total expression of Kit in a dose-dependent manner, whereas the surface expression of FcRI, FcRI, and FcRII was not affected. TGF-β inhibited degranulation and cytokine production, but not PGD₂ production. TGF-β diminished surface Kit expression through a TGF-RI kinase/Smad-dependent pathway by inhibiting new synthesis of Kit protein, which became evident following internalization and degradation of Kit after mast cells were exposed to the Kit ligand, stem cell factor. In contrast, addition of TGF-β had no discernible effect on surface Kit expression when administered 3 days after stem cell factor, by which time surface Kit levels had returned to baseline. Although both transcription and translation are important for de novo expression of Kit, Kit mRNA levels were not affected by TGF-β. Therefore, transcription of a gene other than Kit might be involved in Kit expression. Finally, activation of mast cells increased their susceptibility to TGF-β-mediated apoptosis, a process that might regulate the survival of activated mast cells in vivo.

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 in part by National Institutes of Health Grants R01-AI27517 (to L.B.S.) and K08-AI057357 (to W.Z.), and by a grant from Philip Morris USA and Philip Morris International (to L.B.S.).

² Address correspondence and reprint requests to Dr. Lawrence B. Schwartz, Virginia Commonwealth University, P.O. Box 980263, Richmond, VA 23298. E-mail address: lbschwar{at}vcu.edu

³ Abbreviations used in this paper: SCF, stem cell factor; Cox, cyclooxygenase; Ct, cycle threshold; FAM-VAD-FMK, carboxyfluorescein-Val-Ala-Asp-fluoromethyl ketone; PKC, protein kinase C.