title: BAI, a 3-aminoindazole derivative, inhibits interleukin-1β-induced expression             of cyclooxygenase-2 in A549 human airway cells.
abstract: Cyclooxygenase (COX)-2 and its products, including PGE2, are key inflammatory             mediators. In this study, we have assessed the pharmacological characteristics             of BAI, a 3-aminoindazole derivative and a novel cyclin-dependent kinase (CDK)             inhibitor, for regulation of COX-2 expression induced by interleukin (IL)-1β in             A549 human airway cells. Treatment with BAI strongly inhibited IL-1β-induced expression             of COX-2 at both the protein and mRNA levels. Results of luciferase experiments             also revealed that BAI treatment reduced IL-1β-induced COX-2 promoter activity.             Distinctly, treatment with BAI did not affect IL-1β-induced phospho-rylation of             extracellular signal-regulated protein kinase-1/2 (ERK-1/2), p38 mitogen-activated             protein kinase (MAPK), and c-Jun N-terminal protein kinase-1/2 (JNK-1/2) and proteolysis             of IκB-α, an inhibitor of nuclear factor (NF)-κB, but inhibited IL-1β-induced             phosphorylation of histone H1, a target for phosphorylation by CDKs. siRNA transfection             experiments demonstrated that knockdown of CDK2 and CDK4 led to a slight reduction             of IL-1β-induced histone H1 phosphorylation but had no effect on IL-1β-induced             COX-2 expression. Interestingly, additional cell culture experiments showed the             ability of BAI to repress the PMA-induced COX-2 expression in A549 cells and serum-dependent             COX-2 expression in NCI-H292 cells, a human laryngeal cell line. Collectively,             these results demonstrate firstly that BAI downregulates IL-1β-induced COX-2 expression             through transcriptional repression, which appears to be independent of CDK2, CDK4,             MAPKs and NF-κB, in A549 cells. It is suggested that BAI may be a potential candidate             for treatment of the airway inflammatory diseases where COX-2 overexpression is             problematic.
authors.affiliation: Department of Medical Genetic Engineering, Keimyung University,                     Dalseo-gu, Daegu 704-701, Republic of Korea.
authors.forename: Hua
authors.initials: H
authors.lastname: Hong
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Park
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
authors.forename: Jinho
authors.initials: J
authors.lastname: Lee
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Hong
authors.forename: Gy-Young
authors.initials: GY
authors.lastname: Park
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
mesh_terms: D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007191:Indazoles / Q000737:chemistry / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D020871:RNA Stability / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D053778:Thiazolidines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C545562:2-(1,1'-biphenyl)-4-yl-N-(5-(1,1-dioxo-1lambda(6)-isothiazolidin-2-yl)-1H-indazol-3-yl)acetamide; D052246:Cyclooxygenase 2 Inhibitors; D020672:I-kappa B Proteins; D007191:Indazoles; D053583:Interleukin-1beta; D053778:Thiazolidines; D051546:Cyclooxygenase 2; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D020928:Mitogen-Activated Protein Kinases