Inhibition of matrix metalloproteinases protects mice from ascending infection and chronic disease manifestations resulting from urogenital Chlamydia muridarum infection.
Matrix metalloproteinases (MMP) are a family of host-derived enzymes involved in the turnover of extracellular matrix molecules. We have previously reported enhanced expression of matrix metalloproteinases in Chlamydia muridarum urogenital tract infection of female mice. Kinetics and patterns of MMP expression as well as enhanced expression in susceptible strains of mice in the prior study implied a role for MMP in pathogenesis. To explore this further, we infected a susceptible strain of mice (C3H/HeN) with C. muridarum and treated two groups of mice with either one of two chemical inhibitors of MMP (MMPi; captopril and a chemically modified tetracycline) and reserved infected sham-treated mice as controls. Neither of the treatments affected shedding of viable chlamydiae from the lower urogenital tract, but the administration of either MMPi protected mice from the formation of hydrosalpinx-a surrogate marker of oviduct occlusion and infertility. Interestingly, the mechanism of protection for mice treated with chemically modified tetracycline 3, appeared to be related to prevention of ascending upper genital tract infection. These results imply that MMP are involved in pathogenesis of chlamydial infection in this model by mediating ascension of the infection into the upper genital tract.
Imtiaz
Muhammad T
MT
Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, 555 31st St., Downers Grove, IL 60516, USA. kramse@midwestern.edu
Schripsema
Justin H
JH
Sigar
Ira M
IM
Kasimos
John N
JN
Ramsey
Kyle H
KH
D000818:Animals; D002216:Captopril / Q000008:administration & dosage; D002690:Chlamydia Infections / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D023502:Chlamydia muridarum; D002908:Chronic Disease; D005260:Female; D052776:Female Urogenital Diseases / Q000201:enzymology / Q000382:microbiology / Q000517:prevention & control*; D006877:Hydroxamic Acids / Q000008:administration & dosage; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008817:Mice, Mutant Strains; D009842:Oligopeptides / Q000008:administration & dosage; D013752:Tetracycline / Q000008:administration & dosage
C095170:4-aminobenzoyl-glycyl-prolyl-leucyl-alanine hydroxamic acid; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; D002216:Captopril; D013752:Tetracycline