title: Aspirin Inhibits LPS-Induced Expression of PI3K/Akt, ERK, NF-κB, CX3CL1, and MMPs in Human Bronchial Epithelial Cells.
abstract: This study focused on the effects of aspirin on lipopolysaccharide (LPS)-induced expression of phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt), extracellular signal-regulated protein kinase (ERK), nuclear factor-κB (NF-κB), CX3CL1, and MMPs in human bronchial epithelial cells. Human bronchial epithelial cells were seeded in six-well plates. After 24 h, the cells were classified into six groups: control blank (CK) group; LPS group; PD98059 (ERK inhibitor) (PD) group, treated with LPS + ERK inhibitor; LY294002(PI3K/Akt inhibitor) (LY) group, treated with LPS + PI3K/Akt inhibitor; Aspirin (Asp) group, treated with LPS + aspirin; and Pyrrolidinedithiocarbamic acid (PDTC) group, treated with LPS + NF-κB inhibitor. After 4-h treatment, the cells were harvested. Western blot analysis was performed to detect the expression of PI3K/Akt, ERK, NF-κB, and CX3CL1. Real-time quantitative PCR (RT-qPCR) was used to determine the gene expression of MMP-7, MMP-9, and MMP-12. Compared to the CK group, expression of PI3K/Akt, ERK, NF-κB, and CX3CL1 was significantly increased in the LPS group (P < 0.05). When compared to the LPS group, expression of PI3K/Akt, ERK, NF-κB, and CX3CL1 was significantly decreased in the PD group, PDTC group, and Asp group (P < 0.05). In addition, expression of NF-κB in the LY group was significantly reduced by comparison with the LPS group (P < 0.05). RT-qPCR: When compared to the LPS group, expression of MMP-7 and MMP-12 was significantly decreased in Asp group (P < 0.05). Expression of MMP-12 was significantly reduced in LY group (P < 0.05). LPS-ERK, NF-κB-PI3K/Akt, and CX3CL1 signal pathways exist in human bronchial epithelial cells. The PI3K/Akt inhibitor repressed expression of MMP-12. Aspirin inhibited LPS-induced expression of PI3K, Akt, ERK, NF-κB, CX3CL1, MMP-7, and MMP-12 in human bronchial epithelial cells.
authors.affiliation: ICU Department, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China.
authors.forename: Ronglin
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Wei
authors.affiliation: ICU Department, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China.
authors.forename: Meifei
authors.initials: M
authors.lastname: Zhu
authors.affiliation: ICU Department, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China.
authors.forename: Jiannong
authors.initials: J
authors.lastname: Wu
authors.affiliation: ICU Department, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China. wlc501@139.com.
authors.forename: Lingcong
authors.initials: L
authors.lastname: Wang
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001980:Bronchi / Q000378:metabolism*; D002460:Cell Line; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin; D054428:Chemokine CX3CL1; D002867:Chromones; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D008070:Lipopolysaccharides; D053508:Matrix Metalloproteinase 12; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9; D009025:Morpholines; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011759:Pyrrolidines; D013859:Thiocarbamates; C515538:CX3CL1 protein, human; C020972:pyrrolidine dithiocarbamic acid; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C060932:MMP7 protein, human; C579270:MMP9 protein, human; C507122:MMP12 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: CX3CL1; MMP; NF-κB; aspirin; pI3K/Akt