Unknown

Dataset Information

0

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.


ABSTRACT: 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.

SUBMITTER: Xia Y 

PROVIDER: S-EPMC84809 | biostudies-literature | 1999 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

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.

Xia Y Y   Chen S S   Wang Y Y   Mackman N N   Ku G G   Lo D D   Feng L L  

Molecular and cellular biology 19991101 11


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 ex  ...[more]

Similar Datasets

| S-EPMC1723909 | biostudies-other
| S-EPMC6792909 | biostudies-literature
| S-EPMC2700944 | biostudies-literature
| S-EPMC2895809 | biostudies-literature
| S-EPMC3089558 | biostudies-literature
| S-EPMC3707494 | biostudies-literature
| S-EPMC4948979 | biostudies-literature
| S-EPMC1221534 | biostudies-other
| S-EPMC4710740 | biostudies-literature
| S-EPMC3058966 | biostudies-literature