It is clear that opioid receptors play a role in the regulation of the immune response, including resistance to a number of infectious agents. The opioids modulate the expression of chemokines and chemokine receptors which are critical both for normal immune responses, as well as for the host-parasite interactions associated with AIDS. It has become clear that the opioids can alter susceptibility to infection by HIV. We propose studies in this grant application which should provide a better understanding of the nature of the effects of opioids on the immune system. It is our hypothesis that the opioids selectively alter the production of cytokines that in turn regulate critical chemokine and chemokine receptor expression. We propose studies to clarify the mechanism(s) of the opioid-modulation of essential chemokines and their receptors, with particular emphasis on chemokines which are likely to play a role in susceptibility to infection by HIV. Our findings suggest that an important part of the modulation of immune function by the opioids is to promote the expression of transforming growth factor-beta (TGFbeta), a cytokine which plays an important role in the regulation of virtually all cells of the immune system. We intend to examine the molecular basis for the induction of TGFbeta by the opioids. We also propose to evaluate the molecular mechanisms involved in the TGFbeta-modulation of chemokine and chemokine receptor expression. We expect the proposed studies will enhance our understanding of the role of opioid drugs of abuse in the interaction of the immune system with HIV.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Sharp, Charles
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Temple University
Schools of Medicine
United States
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Rogers, Thomas J (2012) The molecular basis for neuroimmune receptor signaling. J Neuroimmune Pharmacol 7:722-4
Zhang, Lily; Belkowski, Judith Sliker; Briscoe, Tammi et al. (2012) Regulation of mu opioid receptor expression in developing T cells. J Neuroimmune Pharmacol 7:835-42
Kaminsky, David E; Rogers, Thomas J (2011) Nociceptin/orphanin FQ receptor-driven heterologous desensitization of the major HIV-1 co-receptor CXCR4. J Neuroimmune Pharmacol 6:546-50
Finley, Matthew J; Steele, Amber; Cornwell, William D et al. (2011) Transcriptional regulation of the major HIV-1 coreceptor, CXCR4, by the kappa opioid receptor. J Leukoc Biol 90:111-21
Finley, Matthew J; Chen, Xiaohong; Bardi, Guiseppe et al. (2008) Bi-directional heterologous desensitization between the major HIV-1 co-receptor CXCR4 and the kappa-opioid receptor. J Neuroimmunol 197:114-23
Kaminsky, David E; Rogers, Thomas J (2008) Suppression of CCL2/MCP-1 and CCL5/RANTES expression by nociceptin in human monocytes. J Neuroimmune Pharmacol 3:75-82
Happel, Christine; Steele, Amber D; Finley, Matthew J et al. (2008) DAMGO-induced expression of chemokines and chemokine receptors: the role of TGF-beta1. J Leukoc Biol 83:956-63
Finley, M J; Happel, C M; Kaminsky, D E et al. (2008) Opioid and nociceptin receptors regulate cytokine and cytokine receptor expression. Cell Immunol 252:146-54
Chen, Xiaohong; Geller, Ellen B; Rogers, Thomas J et al. (2007) Rapid heterologous desensitization of antinociceptive activity between mu or delta opioid receptors and chemokine receptors in rats. Drug Alcohol Depend 88:36-41
Chen, Xiaohong; Geller, Ellen B; Rogers, Thomas J et al. (2007) The chemokine CX3CL1/fractalkine interferes with the antinociceptive effect induced by opioid agonists in the periaqueductal grey of rats. Brain Res 1153:52-7

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