PAI-1 inhibits development of chronic otitis media and tympanosclerosis in a mouse model of otitis media. (December 2014)

• Record Type: Journal Article
• Authors: Shin, Seul Gi; Koh, Seo Hyun; Woo, Chang-Hoon; Lim, Jae Hyang
• Is Part Of: Acta oto-laryngologica. Volume 134:Number 12(2014)
• Page Start: 1231
• Page End: 1238
• Publication Date: 2014-12
• Subjects: Otolaryngology -- Periodicals; Ear -- Diseases -- Periodicals; Throat -- Diseases -- Periodicals; Otolaryngology -- Electronic Resources; Otorhinolaryngologic Diseases; 617.8
• DOI: 10.3109/00016489.2014.940554
• Languages: English
• ISSNs: 0001-6489

Abstract

<abstract> <title>Abstract</title> <p> <italic>Conclusion:</italic> 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. <italic>Objective:</italic> To investigate the role of PAI-1 in the pathogenesis of OM and subsequent tympanosclerosis. <italic>Methods:</italic> 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. <italic>Results:</italic> 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.</p> </abstract>