PAI-1 inhibits development of chronic otitis media and tympanosclerosis in a mouse model of otitis media

Seul G.i. Shin, Seo H.yun Koh, Chang Hoon Woo, Jae H.yang Lim

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)1231-1238
Number of pages8
JournalActa Oto-Laryngologica
Volume134
Issue number12
DOIs
StatePublished - 1 Dec 2014

Keywords

  • inflammation
  • Nontypable Haemophilus influenzae
  • type 1 plasminogen activator inhibitor

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