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Beta2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappaB-independent mechanisms.

Publication ,  Journal Article
Tan, KS; Nackley, AG; Satterfield, K; Maixner, W; Diatchenko, L; Flood, PM
Published in: Cell Signal
February 2007

Activation of the beta(2) adrenergic receptor (beta(2)AR) located on macrophages has been reported to possess anti-inflammatory properties, inhibiting nuclear factor kappaB (NF-kappaB) activation and cytokine production induced by pro-inflammatory stimuli. Here, we show that activation of the beta(2)AR in the absence of pro-inflammatory stimuli produced up to an 80- and 8-fold increase in IL-1beta and IL-6 transcripts, respectively, in the RAW 264.7 murine macrophage cell line. This increase in mRNA expression was accompanied by a significant increase in IL-1beta and IL-6 protein production. Pre-treatment of RAW cells with pharmacological inhibitors of protein kinase A (PKA) or NF-kappaB pathway failed to block this cytokine increase. Instead, the beta(2)AR-mediated increase in cytokines required activation of both the B-raf-ERK1/2 and p38 pathways. Treatment of RAW cells with the exchange protein directly activated by cAMP (EPAC) agonist also resulted in the up-regulation of IL-1beta and IL-6 transcripts. Examination of the main transcription factors downstream of the ERK1/2 and p38 signaling revealed that beta(2)AR activation resulted in the stimulation of CRE-, but not C/EBPbeta-, ETS-, or NF-kappaB-dependent transcription. Western blot analysis further showed that among the transcription factors which recognize the CRE-binding site, ATF-1 and ATF-2 but not CREB proteins were phosphorylated in an ERK1/2- and p38-dependent manner. Collectively, these results demonstrate that beta(2)ARs possess pro-inflammatory properties and that their activation leads to IL-1beta and IL-6 production through ERK1/2- and p38-dependent activation of ATF-1 and ATF-2 transcription factors.

Duke Scholars

Published In

Cell Signal

DOI

ISSN

0898-6568

Publication Date

February 2007

Volume

19

Issue

2

Start / End Page

251 / 260

Location

England

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Transfection
  • Signal Transduction
  • Receptors, Adrenergic, beta-2
  • RNA, Messenger
  • Proto-Oncogene Proteins B-raf
  • Phosphorylation
  • NF-kappa B
  • Mitogen-Activated Protein Kinase 3
  • Mice
 

Citation

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MLA
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Tan, K. S., Nackley, A. G., Satterfield, K., Maixner, W., Diatchenko, L., & Flood, P. M. (2007). Beta2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappaB-independent mechanisms. Cell Signal, 19(2), 251–260. https://doi.org/10.1016/j.cellsig.2006.06.007
Tan, Kai Soo, Andrea G. Nackley, Kathryn Satterfield, William Maixner, Luda Diatchenko, and Patrick M. Flood. “Beta2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappaB-independent mechanisms.Cell Signal 19, no. 2 (February 2007): 251–60. https://doi.org/10.1016/j.cellsig.2006.06.007.
Tan KS, Nackley AG, Satterfield K, Maixner W, Diatchenko L, Flood PM. Beta2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappaB-independent mechanisms. Cell Signal. 2007 Feb;19(2):251–60.
Tan, Kai Soo, et al. “Beta2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappaB-independent mechanisms.Cell Signal, vol. 19, no. 2, Feb. 2007, pp. 251–60. Pubmed, doi:10.1016/j.cellsig.2006.06.007.
Tan KS, Nackley AG, Satterfield K, Maixner W, Diatchenko L, Flood PM. Beta2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappaB-independent mechanisms. Cell Signal. 2007 Feb;19(2):251–260.
Journal cover image

Published In

Cell Signal

DOI

ISSN

0898-6568

Publication Date

February 2007

Volume

19

Issue

2

Start / End Page

251 / 260

Location

England

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Transfection
  • Signal Transduction
  • Receptors, Adrenergic, beta-2
  • RNA, Messenger
  • Proto-Oncogene Proteins B-raf
  • Phosphorylation
  • NF-kappa B
  • Mitogen-Activated Protein Kinase 3
  • Mice