HIV-Induced TNF-α Regulates Arachidonic Acid and PGE2 Release from HIV-Infected Mononuclear Phagocytes

Mostafa A. Nokta, Mahmoud I. Hassan, Kimberly A. Loesch, Richard B Pollard

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Arachidonic acid (AA) has been shown to interact with transmembrane signaling pathways involved in T-cell activation. The latter have been shown to be impaired in lymphocytes obtained from HIV-infected patients. In the present study, AA and its metabolite, PGE2, released from differentiating human mononuclear phagocytes in response to HIV infection, and their relationship to HIV replication and TNF-α production were examined. The macrophage (Mø) cultures were more permissive for HIV replication than monocyte (MO) cultures. AA release in response to HIV infection was observed in both MO and Mø with a peak at 24 hr postinfection (p.i.). This AA release was 3.8- and 6-fold that of uninfected MO and Mø cultures, respectively. Supernatants from MO and Mø cultures at the peak of AA production inhibited [3H]thymidine uptake of peripheral blood mononuclear cells in response to PHA by 45 and 54%. At 24 hr p.i., PGE2 production was increased in both MO and Mø cultures. This increase was associated with a 1.2- and 20-fold inhibition of IL-1 production, respectively. TNF release, however, increased through day 14 p.i. Treating mock-infected MO with recombinant TNF-α induced AA release. Monoclonal antibodies to TNF inhibited this release by 80%. TNF (0.01-0.4 μg/ml) added exogenously to MO produced a biphasic pattern of AA release; while low concentrations were stimulatory, higher concentrations were inhibitory. Treating monocyte and macrophage cultures with mAb to TNF-α inhibited the HIV-induced release of AA and PGE2. These findings indicate that HIV-induced TNF-α regulates the release of AA and PGE2, which might provide insight into the mechanisms involved in the pathogenesis of HIV-related disorders.

Original languageEnglish (US)
Pages (from-to)590-600
Number of pages11
JournalVirology
Volume208
Issue number2
DOIs
StatePublished - Apr 20 1995
Externally publishedYes

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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