Skip to main content

NF-kappa B as a central mediator in the induction of TGF-beta in monocytes from patients with idiopathic myelofibrosis: an inflammatory response beyond the realm of homeostasis.

Publication ,  Journal Article
Rameshwar, P; Narayanan, R; Qian, J; Denny, TN; Colon, C; Gascon, P
Published in: J Immunol
August 15, 2000

Immune-mediated mechanisms have been implicated in the etiology of idiopathic bone marrow fibrosis (IMF). However, the mechanism remains poorly defined. Compared with healthy controls, IMF monocytes are overactivated, with increased production of TGF-beta and IL-1. TGF-beta is central to the progression of fibrosis in different organs. In the lung, fibrosis is associated with up-regulation of TGF-beta-inducible genes. Because IL-1 and TGF-beta have pro- and antiinflammatory properties and neither appears to regulate the high levels of each other in IMF, we studied the mechanism of this paradigm. We focused on the role of RelA, a subunit of the transcription factor, NF-kappaB that is associated with inflammatory responses. We transiently knocked out RelA from IMF monocytes with antisense oligonucleotides and showed that RelA is central to IL-1 and TGF-beta production and to the adhesion of IMF monocytes. Because the NF-kappaB family comprises subunits other than RelA, we used aspirin and sodium salicylate to inhibit kinases that activate NF-kappaB and showed effects similar to those of the RelA knockout system. It is unlikely that RelA could be interacting directly with the TGF-beta gene. Therefore, we determined its role in TGF-beta production and showed that exogenous IL-1 could induce TGF-beta and adherence of IMF monocytes despite the depletion of NF-kappaB. The results indicate that IL-1 is necessary for TGF-beta production in IMF monocytes, but NF-kappaB activation is required for the production of endogenous IL-1. Initial adhesion activates NF-kappaB, which led to IL-1 production. Through autocrine means, IL-1 induces TGF-beta production. In total, these reactions maintain overactivation of IMF monocytes.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

August 15, 2000

Volume

165

Issue

4

Start / End Page

2271 / 2277

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Rats
  • Primary Myelofibrosis
  • Oligonucleotides, Antisense
  • NF-kappa B
  • Monocytes
  • Middle Aged
  • Mice
  • Macrophage Activation
  • Ligases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rameshwar, P., Narayanan, R., Qian, J., Denny, T. N., Colon, C., & Gascon, P. (2000). NF-kappa B as a central mediator in the induction of TGF-beta in monocytes from patients with idiopathic myelofibrosis: an inflammatory response beyond the realm of homeostasis. J Immunol, 165(4), 2271–2277. https://doi.org/10.4049/jimmunol.165.4.2271
Rameshwar, P., R. Narayanan, J. Qian, T. N. Denny, C. Colon, and P. Gascon. “NF-kappa B as a central mediator in the induction of TGF-beta in monocytes from patients with idiopathic myelofibrosis: an inflammatory response beyond the realm of homeostasis.J Immunol 165, no. 4 (August 15, 2000): 2271–77. https://doi.org/10.4049/jimmunol.165.4.2271.
Rameshwar, P., et al. “NF-kappa B as a central mediator in the induction of TGF-beta in monocytes from patients with idiopathic myelofibrosis: an inflammatory response beyond the realm of homeostasis.J Immunol, vol. 165, no. 4, Aug. 2000, pp. 2271–77. Pubmed, doi:10.4049/jimmunol.165.4.2271.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

August 15, 2000

Volume

165

Issue

4

Start / End Page

2271 / 2277

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Rats
  • Primary Myelofibrosis
  • Oligonucleotides, Antisense
  • NF-kappa B
  • Monocytes
  • Middle Aged
  • Mice
  • Macrophage Activation
  • Ligases