Type III secretion system of Pseudomonas aeruginosa affects matrix metalloproteinase 12 (MMP-12) and MMP-13 expression via nuclear factor κB signaling in human carcinoma epithelial cells and a pneumonia mouse model = 사람 선상피세포의 MMP-12,13 발현에 영향을 미치는 농농균의 type III 분비시스템

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Title
Type III secretion system of Pseudomonas aeruginosa affects matrix metalloproteinase 12 (MMP-12) and MMP-13 expression via nuclear factor κB signaling in human carcinoma epithelial cells and a pneumonia mouse model = 사람 선상피세포의 MMP-12,13 발현에 영향을 미치는 농농균의 type III 분비시스템
Author(s)
Ji Won Park; Y J Kim; I S Shin; Ok-Kyoung Kwon; J M Hong; N R Shin; Sei-Ryang Oh; U H Ha; J H Kim; Kyung Seop Ahn
Bibliographic Citation
Journal of Infectious Diseases, vol. 214, no. 6, pp. 962-969
Publication Year
2016
Abstract
The type III secretion system (T3SS) in Pseudomonas aeruginosa has been linked to severe disease and poor clinical outcomes in animal and human studies. We aimed to investigate whether the ExoS and ExoT effector proteins of P. aeruginosa affect the expression of matrix metalloproteinase 12 (MMP-12) and MMP-13 via nuclear factor κB (NF-κB) signaling pathways. To understand the T3SS, we used ΔExoS, ΔExoT, and ExsA:ⓒ mutants, as well as P. aeruginosa strain K (PAK)-stimulated NCI-H292 cells. We investigated the effects of ΔExoS, ΔExoT, and ExsA::#x000A9; on the development of pneumonia in mouse models. We examined the effects of ΔExoS, ΔExoT, and ExsA::#x000A9; on MMP-12 and MMP-13 production in NCI-H292 cells. ΔExoS and ΔExoT markedly decreased the neutrophil count in bronchoalveolar lavage fluid, with a reduction in proinflammatory mediators, MMP-12, and MMP-13. ΔExoS and ΔExoT reduced NF-κB phosphorylation, together with MMP-12 and MMP-13 expression in PAK-infected mouse models and NCI-H292 cells. To conclude, P. aeruginosa infection induced the expression of MMPs, and P. aeruginosa T3SS appeared to be a key player in MMP-12 and MMP-13 expression, which is further controlled by NF-κB signaling. These findings might be useful in devising a novel therapeutic approach to chronic pulmonary infections that involves decreasing the ExoS and ExoT levels.
Keyword
matrix metalloproteinase (MMP)-12MMP-13NCI-H292NF-κBPneumoniaPseudomonas aeruginosatype III secretion system
ISSN
0022-1899
Publisher
Oxford Univ Press
DOI
http://dx.doi.org/10.1093/infdis/jiw278
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Bio-Resource Central Bank > 1. Journal Articles
Ochang Branch Institute > 1. Journal Articles
Ochang Branch Institute > Natural Product Research Center > 1. Journal Articles
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