Opioid-induced chemokine expression requires NF-κB activity: the role of PKCζ

Journal of Leukocyte Biology

Christine Happel¹  Thomas J. Rogers¹  Thomas J. Rogers ,3²  Christine Happel ²  Michele Kutzler¹  *¹  Michele Kutzler , and² 

[1] Fels Institute for Cancer Research and Molecular Biology, Center for Substance Abuse Research, and Departments of Microbiology and Immunology and Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA Fels Institute for Cancer Research and Molecular Biology, Fels Institute for Cancer Research and Molecular Biology, Center for Substance Abuse Research, and Departments of Microbiology and Immunology and Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA Center for Substance Abuse Research, and Fels Institute for Cancer Research and Molecular Biology, Center for Substance Abuse Research, and Departments of Microbiology and Immunology and Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA Departments of Microbiology and Immunology and Fels Institute for Cancer Research and Molecular Biology, Center for Substance Abuse Research, and Departments of Microbiology and Immunology and Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA Fels Institute for Cancer Research and Molecular Biology, Center for Substance Abuse Research, and Departments of Microbiology and Immunology and Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA;Fels Institute for Cancer Research and Molecular Biology,  Center for Substance Abuse Research, and Departments of Microbiology and Immunology and Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA

关键词: inflammation;    DAMGO;    CCL2;   

DOI  :  10.1189/jlb.0710402

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown