PAI-1 inhibits development of chronic otitis media and tympanosclerosis in a mouse model of otitis media.
CONCLUSIONS
Bullae of type 1 plasminogen activator inhibitor (PAI-1) knockout (KO) mice showed low levels of inflammation against nontypable Haemophilus influenzae (NTHi) at the early stage of otitis media (OM). However, PAI-1 KO mice fail to terminate inflammation, which may significantly contribute to the development of tympanosclerosis in PAI-1 KO mice.


OBJECTIVE
To investigate the role of PAI-1 in the pathogenesis of OM and subsequent tympanosclerosis.


METHODS
OM was induced with NTHi in PAI-1 KO and background control C57BL/6 mice. mRNA expression of PAI-1, tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA) was measured in the bullae of C57BL/6 mice. mRNA expression of interleukin (IL)-1β, tumor necrosis factor (TNF) α, macrophage inflammatory protein (MIP-2), tPA, and uPA in PAI-1 KO and C57BL/6 mice was compared. Histological changes produced by OM were compared at 1, 3, and 7 days after NTHi inoculation.


RESULTS
NTHi up-regulated the expression of PAI-1 and tPA in the bullae of C57BL/6 mice, but not uPA. mRNA expression of IL-1β, TNFα, and MIP-2 was low in PAI-1 KO mice at early time points, but significantly higher at the later stage of OM. Similarly to the gene expression results, histological changes associated with OM were less at days 1 and 3 in PAI-1 KO mice. However, unlike the gradual resolution of OM pathologies in C57BL/6 mice, PAI-1 KO mice showed significant pathological changes of tympanosclerosis.
Department of Microbiology, Ewha Womans University School of Medicine , Seoul , Korea.
Seul Gi
SG
Shin
Seo Hyun
SH
Koh
Chang-Hoon
CH
Woo
Jae Hyang
JH
Lim
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063371:Myringosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010033:Otitis Media / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017395:Plasminogen Activator Inhibitor 1; D012313:RNA
Nontypable Haemophilus influenzae; inflammation; type 1 plasminogen activator inhibitor