title: Selective inhibition of COX-2 is beneficial to mice infected intranasally with VSV.
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-gamma and IL-12, were also increased in celecoxib-treated mice.
authors.affiliation: Department of Biology, New York University, NY 10003, USA.
authors.forename: Nannan
authors.initials: N
authors.lastname: Chen
authors.forename: Andrew
authors.initials: A
authors.lastname: Restivo
authors.forename: Carol Shoshkes
authors.initials: CS
authors.lastname: Reiss
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D015153:Blotting, Western; D000068579:Celecoxib; D002490:Central Nervous System / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018353:Rhabdoviridae Infections / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000821:virology; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects* / Q000502:physiology
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; D018664:Interleukin-12; D007371:Interferon-gamma; D001094:Arachidonate 5-Lipoxygenase; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D000068579:Celecoxib