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

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.

• Authors: Seul Gi Shin, Seo Hyun Koh, Chang-Hoon Woo, Jae Hyang Lim
• Journal: Acta oto-laryngologica (Acta Otolaryngol) Vol. 134 Issue 12 Pg. 1231-8 (Dec 2014) ISSN: 1651-2251 [Electronic] England
• PMID: 25399881 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Plasminogen Activator Inhibitor 1
• RNA

Topics

• Animals
• Chronic Disease
• Disease Models, Animal
• Follow-Up Studies
• Gene Expression Regulation
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myringosclerosis (genetics, metabolism, pathology)
• Otitis Media (genetics, metabolism, pathology)
• Plasminogen Activator Inhibitor 1 (biosynthesis, genetics)
• RNA (genetics)
• Reverse Transcriptase Polymerase Chain Reaction