Cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 acts as a general inhibitor of inflammatory responses in activated BV-2 microglial cells

Tanuja Koppal, Tatiana V. Petrova, Linda J. Van Eldik

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

15-deoxy-Δ12,14-PGJ2, a cyclopentenone derivative of PGD2, was recently reported [Petrova et al., Proc. Natl. Acad. Sci. USA 96 (1999) 4668- 4673] to suppress inducible nitric oxide synthase (iNOS) production in microglia and mixed glial cultures stimulated with lipopolysaccharide (LPS). We report here that in addition to suppressing iNOS production, 15d-PGJ2 also decreases the production of tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-1β) and cyclooxygenase-2 (COX-2) in LPS-stimulated BV-2 microglial cells, thereby acting as a general inhibitor of microglial activation. Concomitantly, 15d-PGJ2 itself up-regulates the production of the antioxidant enzyme heme oxygenase-1 (HO-1) and increases intracellular total glutathione levels. To test if increased HO-1 levels were involved in the ability of 15d-PGJ2 to block microglial activation, we used a HO-1 inhibitor that could block the activity of HO-1. The presence of the HO-1 inhibitor did not alter the 15d-PGJ2-induced inhibition of LPS-stimulated iNOS and TNFα protein levels, and led to only a partial reduction in the protection offered by 15d-PGJ2 against LPS-induced nitrite production. These results suggest that HO-1 upregulation by 15d-PGJ2 is not the primary pathway responsible for the anti-inflammatory action of 15d-PGJ2 in microglial cells. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)115-121
Number of pages7
JournalBrain Research
Volume867
Issue number1-2
DOIs
StatePublished - Jun 9 2000

Bibliographical note

Funding Information:
These studies were supported in part by NIH grants AG13939 and AG15501(to LVE) and NIH training grant AG00260 (to TK).

Keywords

  • Glial activation
  • Inflammatory cytokine
  • Lipopolysaccharide
  • Nitric oxide synthase
  • Oxidative stress
  • Prostaglandin

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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