COX-2 inhibition affects growth rate of Chlamydia muridarum within epithelial cells.
Chlamydiae alter apoptosis of host target cells, which regulates their growth. Cyclooxygenase-2 (COX-2), the rate-limiting enzyme for prostaglandin E2 (PGE2) production, modulates epithelial cell survival. We addressed whether endogenous PGE2 alters chlamydial growth or apoptosis of epithelial cells infected with Chlamydia muridarum. PGE2 is secreted by infected host cells in the genital tract (GT). Using immunohistochemical techniques, we found that COX-2 enzyme was localized to epithelial cells in the GT in vivo. Pellets of the COX-2 enzyme inhibitor, NS-398, and placebo were implanted in mice subcutaneously and released a constant amount of these chemicals throughout the infection. NS-398-treated mice were found to exhibit 10-fold lower bacterial load than the placebo group on day 3 post infection, suggesting disruption of the chlamydial developmental cycle. To prove this, the human lung adenocarcinoma cell line A549 was then infected with different MOIs of C. muridarum in the presence of multiple concentrations of NS-398 in vitro. There was no difference in inclusion forming units (IFUs) between NS-389-treated and untreated cells. We also found no alterations in C. muridarum IFUs in A549 cells transfected with a 2.0 kb cDNA fragment of human COX-2 cloned in the sense (S) or anti-sense (AS) orientation. However, the inclusion size was reduced and the number of EB was significantly diminished during reinfection in AS-transfected cells. In addition, the absence of COX-2 did not significantly modify apoptosis in infected cells. In total, COX-2 deficiency reduces the infectious burden in vivo and may modulate transmission of the organism.
Liu
Wei
W
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, 10833 Le Conte Avenue, Mailroom A7-149 CHS, Los Angeles, CA 90095-1732, USA.
Dubinett
Steven
S
Patterson
Simie Lavern A
SL
Kelly
Kathleen A
KA
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002690:Chlamydia Infections / Q000382:microbiology; D023502:Chlamydia muridarum / Q000254:growth & development / Q000472:pathogenicity*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology*; D005260:Female; D005831:Genital Diseases, Female / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014621:Vagina / Q000382:microbiology
D051546:Cyclooxygenase 2; D015232:Dinoprostone