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> Bakalkin Georgy
> Knapp Pamela E. >
Morphine exacerbate...
Morphine exacerbates HIV-1 Tat-induced cytokine production in astrocytes through convergent effects on [Ca(2+)](i), NF-kappaB trafficking and transcription
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El-Hage, Nazira (författare)
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Bruce-Keller, Annadora J (författare)
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- Yakovleva, Tatiana (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Molecular neuropsychopharmacology
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- Bazov, Igor (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Molecular neuropsychopharmacology
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- Bakalkin, Georgy (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Molecular neuropsychopharmacology
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Knapp, Pamela E (författare)
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Hauser, Kurt F (författare)
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(creator_code:org_t)
- 2008-12-31
- 2008
- Engelska.
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:12, s. e4093-
- Relaterad länk:
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https://journals.plo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Astroglia are key cellular sites where opiate drug signals converge with the proinflammatory effects of HIV-1 Tat signals to exacerbate HIV encephalitis. Despite this understanding, the molecular sites of convergence driving opiate-accelerated neuropathogenesis have not been deciphered. We therefore explored potential points of interaction between the signaling pathways initiated by HIV-1 Tat and opioids in striatal astrocytes. Profiling studies screening 152 transcription factors indicated that the nuclear factor-kappa B (NF-kappaB) subunit, c-Rel, was a likely candidate for Tat or Tat plus opiate-induced increases in cytokine and chemokine production by astrocytes. Pretreatment with the NF-kappaB inhibitor parthenolide provided evidence that Tat+/-morphine-induced release of MCP-1, IL-6 and TNF-alpha by astrocytes is NF-kappaB dependent. The nuclear export inhibitor, leptomycin B, blocked the nucleocytoplasmic shuttling of NF-kappaB; causing p65 (RelA) accumulation in the nucleus, and significantly attenuated cytokine production in Tat+/-morphine exposed astrocytes. Similarly, chelating intracellular calcium ([Ca(2+)](i)) blocked Tat+/-morphine-evoked MCP-1 and IL-6 release, while artificially increasing the concentration of extracellular Ca(2+) reversed this effect. Taken together, these results demonstrate that: 1) exposure to Tat+/-morphine is sufficient to activate NF-kappaB and cytokine production, 2) the release of MCP-1 and IL-6 by Tat+/-morphine are highly Ca(2+)-dependent, while TNF-alpha appears to be less affected by the changes in [Ca(2+)](i), and 3) in the presence of Tat, exposure to opiates augments Tat-induced NF-kappaB activation and cytokine release through a Ca(2+)-dependent pathway.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- PHARMACY
- FARMACI
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- ref (ämneskategori)
- art (ämneskategori)
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