Journal article
Opioid-induced chemokine expression requires NF-κB activity: the role of PKCζ
Journal of leukocyte biology, v 89(2)
01 Feb 2011
PMID: 20952659
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Mu opioid receptor activation induces the expression of chemokine CCL2 through a pro-inflammatory, PKCζ-dependent, NF-κB pathway.
Opioid receptor agonists induce broad immunomodulatory activity, which substantially alters host defense and the inflammatory response. Previous studies have shown that the MOR selective agonist DAMGO has the capacity to increase the expression of the proinflammatory chemokines CCL2, CCL5, and CXCL10 in human PBMCs. NF-κB is a transcription factor that plays a pivotal role in innate and adaptive immune responses. We report that NF-κB is a vital player in the DAMGO-induced, MOR-mediated regulation of chemokine expression. Results show that NF-κB inhibitors prevent the induction of CCL2 expression in response to DAMGO administration and that the NF-κB subunit, p65, is phosphorylated at serine residues 311 and 536 in response to MOR activation. Furthermore, we demonstrate that PKCζ is phosphorylated following DAMGO-induced MOR activation, and this kinase is essential for NF-κB activation as well as CCL2 expression and transcriptional activity. Finally, ChIP analysis shows that DAMGO administration induces binding of p65 to the enhancer region of the CCL2 promoter. These data are consistent with the notion that MOR activation promotes a proinflammatory response, which involves NF-κB activation. Our results also suggest a significant and novel role for PKCζ as an essential participant in the MOR-mediated regulation of proinflammatory chemokine expression.
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Details
- Title
- Opioid-induced chemokine expression requires NF-κB activity: the role of PKCζ
- Creators
- Christine Happel - Temple UniversityMichele Kutzler - Temple UniversityThomas J. Rogers - Temple University
- Publication Details
- Journal of leukocyte biology, v 89(2)
- Publisher
- Society for Leukocyte Biology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:000286723700013
- Scopus ID
- 2-s2.0-79951818096
- Other Identifier
- 991019173764304721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Cell Biology
- Hematology
- Immunology