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: To determine whether MMP-12 and MMP-13 are necessary for strain K-induced proinflammatory cytokine expression, we transfected cells with siRNAs targeting either MMP-12 or MMP-13 and saw a detectable reduction in protein 24 h after transfection. We have found effects on the expression of MMP-12 and MMP-13 (data not shown). Notably, the induction of proinflammatory cytokines previously observed in response to strain K infection in normal H292 cells was absent in siRNA-transfected cells. Using an ELISA, proinflammatory cytokine expression in response to the IL-1β and TNF-α consensus sequence was also significantly reduced in the presence of proinflammatory cytokine-specific siRNAs in H292 cells (Fig. 8A and B). These data indicate that MMP-12 and MMP-13 are necessary for proinflammatory cytokine expression.
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.