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

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)...

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Published in:The Journal of infectious diseases 2016-09, Vol.214 (6), p.962-969
Main Authors: Park, Ji-Won, Kim, Yong-Jae, Shin, In-Sik, Kwon, Ok-Kyoung, Hong, Ju Mi, Shin, Na-Rae, Oh, Sei-Ryang, Ha, Un-Hwan, Kim, Jae-Hong, Ahn, Kyung-Seop
Format: Article
Language:English
Subjects:
ADP Ribose Transferases - genetics
ADP Ribose Transferases - metabolism
Animals
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bacterial Toxins - genetics
Bacterial Toxins - metabolism
Disease Models, Animal
Epithelial Cells - microbiology
Gene Knockout Techniques
GTPase-Activating Proteins - genetics
GTPase-Activating Proteins - metabolism
Host-Pathogen Interactions
Humans
Matrix Metalloproteinase 12 - biosynthesis
Matrix Metalloproteinase 12 - metabolism
Matrix Metalloproteinase 13 - biosynthesis
Matrix Metalloproteinase 13 - metabolism
Mice
NF-kappa B - metabolism
Pneumonia, Bacterial - microbiology
Pneumonia, Bacterial - pathology
Pseudomonas aeruginosa - pathogenicity
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Signal Transduction
Trans-Activators - genetics
Trans-Activators - metabolism
Type III Secretion Systems - metabolism
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Summary: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::Ω mutants, as well as P. aeruginosa strain K (PAK)-stimulated NCI-H292 cells. We investigated the effects of ΔExoS, ΔExoT, and ExsA::Ω on the development of pneumonia in mouse models. We examined the effects of ΔExoS, ΔExoT, and ExsA::Ω 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.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiw278