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RelB modulation of IkappaBalpha stability as a mechanism of transcription suppression of interleukin-1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in fibroblasts.

Publication ,  Journal Article
Xia, Y; Chen, S; Wang, Y; Mackman, N; Ku, G; Lo, D; Feng, L
Published in: Mol Cell Biol
November 1999

Members of the NF-kappaB/RelB family of transcription factors play important roles in the regulation of inflammatory and immune responses. RelB, a member of this family, has been characterized as a transcription activator and is involved in the constitutive NF-kappaB activity in lymphoid tissues. However, in a previous study we observed an overexpression of chemokines in RelB-deficient fibroblasts. Here we show that RelB is an important transcription suppressor in fibroblasts which limits the expression of proinflammatory mediators and may exert its function by modulating the stability of IkappaBalpha protein. Fibroblasts from relb(-/-) mice overexpress interleukin-1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in response to lipopolysaccharide (LPS) stimulation. These cells have an augmented and prolonged LPS-inducible IKK activity and an accelerated degradation which results in a diminished level of IkappaBalpha protein, despite an upregulated IkappaBalpha mRNA expression. Consequently, NF-kappaB activity was augmented and postinduction repression of NF-kappaB activity was impaired in these cells. The increased kappaB-binding activity and cytokine overexpression was suppressed by introducing RelB cDNA or a dominant negative IkappaBalpha into relb(-/-) fibroblasts. Our findings suggest a novel transcription suppression function of RelB in fibroblasts.

Duke Scholars

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Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

November 1999

Volume

19

Issue

11

Start / End Page

7688 / 7696

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Transcription, Genetic
  • Transcription Factors
  • Transcription Factor RelB
  • RNA, Messenger
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • NF-KappaB Inhibitor alpha
  • Mice, Mutant Strains
 

Citation

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Xia, Y., Chen, S., Wang, Y., Mackman, N., Ku, G., Lo, D., & Feng, L. (1999). RelB modulation of IkappaBalpha stability as a mechanism of transcription suppression of interleukin-1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in fibroblasts. Mol Cell Biol, 19(11), 7688–7696. https://doi.org/10.1128/MCB.19.11.7688
Xia, Y., S. Chen, Y. Wang, N. Mackman, G. Ku, D. Lo, and L. Feng. “RelB modulation of IkappaBalpha stability as a mechanism of transcription suppression of interleukin-1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in fibroblasts.Mol Cell Biol 19, no. 11 (November 1999): 7688–96. https://doi.org/10.1128/MCB.19.11.7688.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

November 1999

Volume

19

Issue

11

Start / End Page

7688 / 7696

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Transcription, Genetic
  • Transcription Factors
  • Transcription Factor RelB
  • RNA, Messenger
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • NF-KappaB Inhibitor alpha
  • Mice, Mutant Strains