title: 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.
abstract: Pseudomonas aeruginosa infections persist in patients with cystic fibrosis (CF) and drive lung disease progression. 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. In this study, we used quantitative bacteriology, histological examination, and proinflammatory cytokine levels to evaluate the effects of MMP-12 and MMP-13 on P. aeruginosa strain K-induced infection and pneumonia in H292 epithelial cells and mice, respectively. Under inflammatory stimulation, mRNA and protein expression levels of proinflammatory mediators were higher in strain K-infected mice and cells than in uninfected counterparts, in which MMP-12 and MMP-13 expression reached levels similar to those observed in epithelial cells. Moreover, we also found that the NF-κB pathway might be involved in the induction of cytokines in response to strain K infection. Taken together, these data suggest that MMP-12 and MMP-13 alter strain K infection in mice and play a role in inflammatory regulation by modulating cytokine levels.
authors.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.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: In-Sik
authors.initials: IS
authors.lastname: Shin
authors.affiliation: Department of Biotechnology and Bioinformatics, Korea University, Sejong, Republic of Korea.
authors.forename: Un-Hwan
authors.initials: UH
authors.lastname: Ha
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, Republic of Korea.
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea jhongkim@korea.ac.kr ksahn@kribb.re.kr.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, Republic of Korea jhongkim@korea.ac.kr ksahn@kribb.re.kr.
authors.forename: Kyung-Seop
authors.initials: KS
authors.lastname: Ahn
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003550:Cystic Fibrosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D053508:Matrix Metalloproteinase 12 / Q000235:genetics / Q000276:immunology*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D053509:Matrix Metalloproteinase 13; D053508:Matrix Metalloproteinase 12; C000602031:matrix metallopeptidase 12, mouse