Selective inhibition of COX-2 is beneficial to mice infected intranasally with VSV

Nannan Chen, Andrew Restivo, Carol Shoshkes Reiss

Research output: Contribution to journalArticle

Abstract

Cyclooxygenase (COX) is the key enzyme for prostaglandin (PG) synthesis. PGs are mediators of many critical physiological and inflammatory responses. There are two isoforms, COX-1 and COX-2, both of which are constitutively expressed in the central nervous system (CNS). Studies have shown that COX-1 and COX-2 are involved in physiological and pathological conditions of the brain. However, little is known about the role(s) of COX in the host defense system against a viral infection in the CNS. In this report, we used Vesicular Stomatitis Virus (VSV) induced acute encephalitis to distinguish between the contribution(s) of the two isoforms. COX-2 activity was inhibited with a COX-2 selective drug, celecoxib (Celebrex™), and COX-1 was antagonized with SC560. We found that inhibition of COX-2 led to decreased viral titers, while COX-1 antagonism did not have the same effect at day 1 post infection. 5-lipooxygenase (5-LO) expression and neutrophil recruitment in the CNS were increased in celecoxib-inhibited mice. Furthermore, mice treated with celecoxib expressed more Nitric Oxide Synthase-1 (NOS-1), a crucial component of the innate immune system in the restriction of VSV propagation. The expression of type 1 cytokines, IFN-γ and IL-12, were also increased in celecoxib-treated mice.

Original languageEnglish (US)
Pages (from-to)143-155
Number of pages13
JournalProstaglandins and Other Lipid Mediators
Volume67
Issue number2
DOIs
StatePublished - 2002

Fingerprint

Celecoxib
Vesicular Stomatitis
Cyclooxygenase 2
Cyclooxygenase 1
Viruses
Neurology
Prostaglandin-Endoperoxide Synthases
Protein Isoforms
Central Nervous System Viral Diseases
Central Nervous System
Neutrophil Infiltration
Immune system
Encephalitis
Interleukin-12
Nitric Oxide Synthase
Prostaglandins
Immune System
Brain
Cytokines

Keywords

  • COX
  • In vivo animal models
  • Inflammatory mediators
  • Neuroimmunology
  • NOS

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Selective inhibition of COX-2 is beneficial to mice infected intranasally with VSV. / Chen, Nannan; Restivo, Andrew; Reiss, Carol Shoshkes.

In: Prostaglandins and Other Lipid Mediators, Vol. 67, No. 2, 2002, p. 143-155.

Research output: Contribution to journalArticle

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