title: [Inhibition of NHE1 down-regulates IL-8 expression and enhances p38 phosphorylation].
abstract: This study was purposed to explore the changes of possible angiogenetic factors other than VEGF after inhibition of NHE1 and their related mechanisms. The K562 cells were treated by NHE1 specific inhibitor cariporide, the angiogenesis factors after inhibition of NHE1 were screened by using protein chip, the IL-8 expression level after cariporide treatment was detected by real-time quantitative PCR; the K562 cells with stable interference of NHE1 were constructed, the IL-8 expression level after interference of NHE1 was detected by real-time quantitative PCR; the p38 phosphorylation level in K562 cells treated with cariporide was detected by Western blot. After treatment of K562 cells with p38 inhibitor SB203580, the IL-8 expression level was decreased by real-time quantitative PCR. The results of protein chip showed that IL-8 expression decreased after cariporide treatment. Real-time quantitative PCR confirmed this inhibitory effect. The p38 phosphorylation level increased after cariporide treatment. The down-regulation of IL-8 expression induced by cariporide treatment was partially restored after K562 cells were treated with p38 inhibitor SB203580. It is concluded that the inhibition of NHE1 can inhibit IL-8 expression through up-regulation of p38 phosphorylation.
authors.affiliation: Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Hai-Rui
authors.initials: HR
authors.lastname: Zhang
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Jin
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chang
authors.forename: Hong-Ju
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Ya-Ni
authors.initials: YN
authors.lastname: Lin
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Li
authors.forename: Rong-Xin
authors.initials: RX
authors.lastname: Ru
authors.forename: Tian-Xiang
authors.initials: TX
authors.lastname: Pang
mesh_terms: D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors*; D015536:Down-Regulation; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D020014:K562 Cells; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; D027682:Cation Transport Proteins; D006146:Guanidines; D007093:Imidazoles; D016209:Interleukin-8; D011725:Pyridines; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580