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TLR agonists regulate PDGF-B production and cell proliferation through TGF-beta/type I IFN crosstalk.

Publication ,  Journal Article
Chow, EK; O'connell, RM; Schilling, S; Wang, X-F; Fu, X-Y; Cheng, G
Published in: EMBO J
December 7, 2005

Transforming growth factor-beta (TGF-beta) and type I interferon (IFN) autocrine/paracrine loops are recognized as key mediators of signaling cascades that control a variety of cellular functions. Here, we describe a novel mechanism by which Toll-like receptor (TLR) agonists utilize these two autocrine/paracrine loops to differentially regulate the induction of PDGF-B, a growth factor implicated in a number of diseases ranging from tumor metastasis to glomerulonephritis. We demonstrate that CpG-specific induction of PDGF-B requires activation of Smads through TGFbeta1 autocrine/paracrine signaling. In contrast, polyinosinic:polycytidylic acid strongly represses CpG's as well as its own intrinsic ability to induce PDGF-B mRNA through type I IFN-mediated induction of Smad7, a negative regulator of Smad3/4. Furthermore, we have shown that this crosstalk mechanism translates into similar regulation of mesangial cell proliferation. Thus, our results demonstrate the importance of crosstalk between TGF-beta and type I IFNs in determining the specificity of TLR-mediated gene induction.

Duke Scholars

Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

December 7, 2005

Volume

24

Issue

23

Start / End Page

4071 / 4081

Location

England

Related Subject Headings

  • Up-Regulation
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • Toll-Like Receptors
  • Smad7 Protein
  • Smad4 Protein
  • Signal Transduction
  • Receptors, Immunologic
  • RNA, Messenger
  • Proto-Oncogene Proteins c-sis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chow, E. K., O’connell, R. M., Schilling, S., Wang, X.-F., Fu, X.-Y., & Cheng, G. (2005). TLR agonists regulate PDGF-B production and cell proliferation through TGF-beta/type I IFN crosstalk. EMBO J, 24(23), 4071–4081. https://doi.org/10.1038/sj.emboj.7600867
Chow, Edward K., Ryan M. O’connell, Stephen Schilling, Xiao-Fan Wang, Xin-Yuan Fu, and Genhong Cheng. “TLR agonists regulate PDGF-B production and cell proliferation through TGF-beta/type I IFN crosstalk.EMBO J 24, no. 23 (December 7, 2005): 4071–81. https://doi.org/10.1038/sj.emboj.7600867.
Chow EK, O’connell RM, Schilling S, Wang X-F, Fu X-Y, Cheng G. TLR agonists regulate PDGF-B production and cell proliferation through TGF-beta/type I IFN crosstalk. EMBO J. 2005 Dec 7;24(23):4071–81.
Chow, Edward K., et al. “TLR agonists regulate PDGF-B production and cell proliferation through TGF-beta/type I IFN crosstalk.EMBO J, vol. 24, no. 23, Dec. 2005, pp. 4071–81. Pubmed, doi:10.1038/sj.emboj.7600867.
Chow EK, O’connell RM, Schilling S, Wang X-F, Fu X-Y, Cheng G. TLR agonists regulate PDGF-B production and cell proliferation through TGF-beta/type I IFN crosstalk. EMBO J. 2005 Dec 7;24(23):4071–4081.

Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

December 7, 2005

Volume

24

Issue

23

Start / End Page

4071 / 4081

Location

England

Related Subject Headings

  • Up-Regulation
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • Toll-Like Receptors
  • Smad7 Protein
  • Smad4 Protein
  • Signal Transduction
  • Receptors, Immunologic
  • RNA, Messenger
  • Proto-Oncogene Proteins c-sis