Journal
ARTHRITIS AND RHEUMATISM
Volume 58, Issue 5, Pages 1485-1495Publisher
WILEY
DOI: 10.1002/art.23371
Keywords
-
Categories
Funding
- NIAMS NIH HHS [R01-AR-052748] Funding Source: Medline
Ask authors/readers for more resources
Objective. Recent studies have implicated products of cyclooxygenase 2 (COX-2) in not only induction hut also resolution of the inflammatory response; however, the contribution of COX-2 products to the in vivo response to infection is unknown. The aim of this study was to determine the contribution of COX-2 to temporal regulation of the inflammatory response to infection in a murine model of Lyme arthritis. Methods. Experimental Lyme disease was induced in both arthritis-resistant DBA/2J and arthritissusceptible C3H/HeJ mice by inoculation in the hind footpads with Borrelia burgdorferi. COX-2 inhibitors were administered daily, and their effect on arthritis pathology was assessed at various time points postinfection. The COX-2 deficiency was also backcrossed onto both DBA and C3H backgrounds to confirm the findings from COX-2 inhibitor-treated mice. Results. In COX-2 inhibitor-treated or COX-2(-/-) C3H mice, arthritis developed normally but did not resolve. Cessation of COX-2 inhibitor treatment on day 14 postinfection did not induce resolution of arthritis, indicating an early onset for the molecular mechanisms governing resolution. The lack of resolution of arthritis correlated with altered COX-2 and cytosolic phospholipase A(2) messenger RNA levels in the joints of C3H mice. In addition, the proresolution lipid molecule 15-deoxy-Delta(12,14)-prostaglandin J(2) was produced in response to B burgdorferi infection, and its production was attenuated by the inhibition of COX-2. Conclusion. Our results demonstrate that early production of COX-2 products is necessary for resolution of the inflammatory arthritis induced by Borrelia infection, and that COX-2 inhibition may result in prolonged inflammatory states, possibly by inhibition of proresolution eicosanoids.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available