PMID- 15630704
OWN - NLM
STAT- MEDLINE
DCOM- 20050516
LR  - 20220318
IS  - 0894-1491 (Print)
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 50
IP  - 2
DP  - 2005 Apr 15
TI  - Synergistic increases in intracellular Ca2+, and the release of MCP-1, RANTES, 
      and IL-6 by astrocytes treated with opiates and HIV-1 Tat.
PG  - 91-106
AB  - Recent evidence suggests that injection drug users who abuse heroin are at 
      increased risk of CNS complications from human immunodeficiency virus (HIV) 
      infection. Opiate drugs may intrinsically alter the pathogenesis of HIV by 
      directly modulating immune function and by directly modifying the CNS response to 
      HIV. Despite this, the mechanisms by which opiates increase the neuropathogenesis 
      of HIV are uncertain. In the present study, we describe the effect of morphine 
      and the HIV-1 protein toxin Tat(1-72) on astroglial function in cultures derived 
      from ICR mice. Astroglia maintain the blood-brain barrier and influence 
      inflammatory signaling in the CNS. Astrocytes can express mu-opioid receptors, 
      and are likely targets for abused opiates, which preferentially activate 
      mu-opioid receptors. While Tat alone disrupts astrocyte function, when combined 
      with morphine, Tat causes synergistic increases in [Ca(2+)](i). Moreover, 
      astrocyte cultures treated with morphine and Tat showed exaggerated increases in 
      chemokine release, including monocyte chemoattractant protein-1 (MCP-1) and 
      regulated on activation, normal T cell expressed and secreted (RANTES), as well 
      as interleukin-6 (IL-6). Morphine-Tat interactions were prevented by the 
      mu-opioid receptor antagonist beta-funaltrexamine, or by immunoneutralizing 
      Tat(1-72) or substituting a nontoxic, deletion mutant (Tat(Delta31-61)). Our 
      findings suggest that opiates may increase the vulnerability of the CNS to viral 
      entry (via recruitment of monocytes/macrophages) and ensuing HIV encephalitis by 
      synergistically increasing MCP-1 and RANTES release by astrocytes. The results 
      further suggest that astrocytes are key intermediaries in opiate-HIV interactions 
      and disruptions in astroglial function and inflammatory signaling may contribute 
      to an accelerated neuropathogenesis in HIV-infected individuals who abuse 
      opiates.
CI  - (c) 2004 Wiley-Liss, Inc.
FAU - El-Hage, Nazira
AU  - El-Hage N
AD  - Department of Anatomy and Neurobiology, University of Kentucky College of 
      Medicine, Lexington, Kentucky 40536-0298, USA.
FAU - Gurwell, Julie A
AU  - Gurwell JA
FAU - Singh, Indrapal N
AU  - Singh IN
FAU - Knapp, Pamela E
AU  - Knapp PE
FAU - Nath, Avindra
AU  - Nath A
FAU - Hauser, Kurt F
AU  - Hauser KF
LA  - eng
GR  - P20 RR015592/RR/NCRR NIH HHS/United States
GR  - R01 DA013728/DA/NIDA NIH HHS/United States
GR  - DA13728/DA/NIDA NIH HHS/United States
GR  - P20RR015592/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Analgesics, Opioid)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Cytokines)
RN  - 0 (Gene Products, tat)
RN  - 0 (Interleukin-6)
RN  - 0 (Narcotics)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Opioid, mu)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
RN  - 76I7G6D29C (Morphine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Analgesics, Opioid/pharmacology
MH  - Animals
MH  - Astrocytes/drug effects/*metabolism
MH  - Calcium/metabolism/*pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Chemokine CCL5/*metabolism
MH  - Cytokines/metabolism
MH  - Drug Synergism
MH  - Gene Products, tat/*metabolism
MH  - HIV-1/*metabolism
MH  - Homeostasis/physiology
MH  - Humans
MH  - Interleukin-6/*metabolism
MH  - Kinetics
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Microglia/metabolism
MH  - Morphine/pharmacology
MH  - Narcotics/*pharmacology
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Receptors, Opioid, mu/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects
MH  - tat Gene Products, Human Immunodeficiency Virus
PMC - PMC4301446
MID - NIHMS655651
EDAT- 2005/01/05 09:00
MHDA- 2005/05/17 09:00
PMCR- 2015/01/21
CRDT- 2005/01/05 09:00
PHST- 2005/01/05 09:00 [pubmed]
PHST- 2005/05/17 09:00 [medline]
PHST- 2005/01/05 09:00 [entrez]
PHST- 2015/01/21 00:00 [pmc-release]
AID - 10.1002/glia.20148 [doi]
PST - ppublish
SO  - Glia. 2005 Apr 15;50(2):91-106. doi: 10.1002/glia.20148.