Pathophysiological changes induced by Pseudomonas aeruginosa infection are involved in MMP-12 and MMP-13 upregulation in human carcinoma epithelial cells and a pneumonia mouse model.
Bottom Line: P. aeruginosa potently activates the innate immune system mostly through the recognition of pathogen-associated molecular patterns, such as flagellin.Matrix metalloproteinases 12 and 13 (MMP-12 and MMP-13, respectively) exacerbate chronic lung infection and inflammation by promoting uncontrolled tissue rearrangements and fibrosis, yet the underlying molecular mechanisms by which this occurs remain largely unknown.Moreover, we also found that the NF-κB pathway might be involved in the induction of cytokines in response to strain K infection.
Affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, Republic of Korea College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.Show MeSH
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Mentions: We investigated the effects of NF-κB signaling on the production of MMP-12 and MMP-13 induced by strain K by using NF-κB inhibitors, including BAY-11-7082. BAY-11-7082 (Calbiochem, Merck, Darmstadt, Germany) is an inhibitor of IκB-α phosphorylation. BAY-11-7082, a potential anti-inflammatory agent, is an irreversible inhibitor of cytokine-inducible IκB-α phosphorylation (50% inhibitory concentration [IC50], 10 μM) (21). The NF-κB inhibitor BAY-11-7082 has no effect on the growth of strain K (data not shown). BAY-11-7082 notably blocked the strain K-induced increase in MMP-12 and MMP-13 mRNA (Fig. 2A and B) and protein (Fig. 2C and D) expression. Moreover, BAY-11-7082 inhibited the phosphorylation of the NF-κB p65 subunit and IκB-α that occurs in response to strain K infection of H292 cells (Fig. 3A). This finding was also confirmed by luciferase assay (Fig. 3B) and IHC (Fig. 3C). Accordingly, pretreatment of the cells with BAY-11-7082 (10 μM, 1 h), a specific IκB-α inhibitor, blocked NF-κB p65 activation induced by strain K infection.
Affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, Republic of Korea College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.