Morphine enhances Tat-induced activation in murine microglia.
There is increasing evidence that opiates accelerate the pathogenesis and progression of acquired immunodeficiency syndrome (AIDS), as well as the incidence of human immunodeficiency virus (HIV) encephalitis (HIVE), a condition characterized by inflammation, leukocyte infiltration, and microglial activation. The mechanisms, by which the HIV-1 transactivating protein Tat and opioids exacerbate microglial activation, however, are not fully understood. In the current study, we explored the effects of morphine and HIV-1 Tat(1-72) on the activation of mouse BV-2 microglial cells and primary mouse microglia. Both morphine and Tat exposure caused up-regulation of the chemokine receptor CCR5, an effect blocked by the opioid receptor antagonist naltrexone. Morphine in combination with Tat also induced morphological changes in the BV-2 microglia from a quiescent to an activated morphology, with a dramatic increase in the expression of the microglial activation marker CD11b, as compared with cells exposed to either agent alone. In addition, the mRNA expression of inducible nitric oxide synthase (iNOS), CD40 ligand, Interferon-gamma-inducible protein 10 (IP-10), and the proinflammatory cytokines tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6, which were elevated with Tat alone, were dramatically enhanced with Tat in the presence of morphine. In summary, these findings shed light on the cooperative effects of morphine and HIV-1 Tat on both microglial activation and HIV coreceptor up-regulation, effects that could result in exacerbated neuropathogenesis.
Bokhari
Sirosh M
SM
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Yao
Honghong
H
Bethel-Brown
Crystal
C
Fuwang
Peng
P
Williams
Rachel
R
Dhillon
Navneet K
NK
Hegde
Ramakrishna
R
Kumar
Anil
A
Buch
Shilpa J
SJ
D015526:AIDS Dementia Complex; D000701:Analgesics, Opioid; D000818:Animals; D039481:CD11b Antigen / Q000096:biosynthesis; D002478:Cells, Cultured; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D009020:Morphine / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000096:biosynthesis; D015854:Up-Regulation; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism* / Q000494:pharmacology
D000701:Analgesics, Opioid; D039481:CD11b Antigen; D019713:Receptors, CCR5; D054322:tat Gene Products, Human Immunodeficiency Virus; C470431:tat peptide (1-72), Human immunodeficiency virus 1; D009020:Morphine