title: NPS2143 Inhibits MUC5AC and Proinflammatory Mediators in Cigarette Smoke Extract (CSE)-Stimulated Human Airway Epithelial Cells.
abstract: Mucus overproduction is a fundamental hallmark of COPD that is caused by exposure to cigarette smoke. MUC5AC is one of the main mucin genes expressed in the respiratory epithelium, and its transcriptional upregulation often correlates with increased mucus secretion. Calcium-sensing receptor (CaSR) antagonists have been reported to possess anti-inflammatory effects. The purpose of the present study was to investigate the protective role of NPS2143, a selective CaSR antagonist on cigarette smoke extract (CSE)-stimulated NCI-H292 mucoepidermoid human lung cells. Treatment of NPS2143 significantly inhibited the expression of MUC5AC in CSE-stimulated H292 cells. NPS2143 reduced the expression of MMP-9 in CSE-stimulated H292 cells. NPS2143 also decreased the release of proinflammatory cytokines such as IL-6 and TNF-α in CSE-stimulated H292 cells. Furthermore, NPS2143 attenuated the activation of MAPKs (JNK, p38, and ERK) and inhibited the nuclear translocation of NF-κB in CSE-stimulated H292 cells. These results indicate that NPS2143 had a therapeutic potential in COPD.
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk, 363-883, Republic of Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk, 363-883, Republic of Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk, 363-883, Republic of Korea.|Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, 305-764, Republic of Korea.
authors.forename: Ok-Kyoung
authors.initials: OK
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Kangwon, 200-701, Republic of Korea.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, 305-764, Republic of Korea.
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
authors.affiliation: Department of Life Sciences and Biotechnology, Korea University, 5-1 Anam-dong, Sungbuk-gu, Seoul, 136-701, Republic of Korea.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk, 363-883, Republic of Korea. seiryang@kribb.re.kr.
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk, 363-883, Republic of Korea. ksahn@kribb.re.kr.
authors.forename: Kyoung-Seop
authors.initials: KS
authors.lastname: Ahn
mesh_terms: D021581:Active Transport, Cell Nucleus; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D055271:Mucin 5AC / Q000037:antagonists & inhibitors* / Q000235:genetics; D009093:Mucus / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D055271:Mucin 5AC; C436740:N-(2-hydroxy-3-(2-cyano-3-chlorophenoxy)propyl)-1,1-dimethyl-2-(2-nephthyl)ethylamine; D016328:NF-kappa B; D009281:Naphthalenes; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: MAPKs; MUC5AC; NF-κB; NPS2143; chronic obstructive pulmonary disease; cigarette smoke