PMID- 28800474 OWN - NLM STAT- MEDLINE DCOM- 20171107 LR - 20220408 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 90 DP - 2017 Oct TI - NPS 2143, a selective calcium-sensing receptor antagonist inhibits lipopolysaccharide-induced pulmonary inflammation. PG - 150-157 LID - S0161-5890(17)30442-X [pii] LID - 10.1016/j.molimm.2017.07.012 [doi] AB - NPS 2143, a novel and selective antagonist of calcium-sensing receptor (CaSR) has been reported to possess anti-inflammatory activity. In the present study, we examined the protective effect of NPS 2143 on lipopolysaccharide (LPS)-induced acute lung injury (ALI). NPS 2143 pretreatment significantly inhibited the influx of inflammatory cells and the expression of monocyte chemoattractant protein-1 (MCP-1) in the lung of mice with LPS-induced ALI. NPS 2143 decreased the levels of neutrophil elastase (NE) and protein concentration in the bronchoalveolar lavage fluid (BALF). NPS 2143 also reduced the production of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the BALF and serum. In addition, NPS 2143 attenuated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and increased the activation of AMP-activated protein kinase (AMPK) in the lung. NPS 2143 also downregulated the activation of nuclear factor-kappa B (NF-kappaB) in the lung. In LPS-stimulated H292 airway epithelial cells, NPS 2143 attenuated the releases of IL-6 and MCP-1. Furthermore, NPS 2143 upregulated the activation of AMPK and downregulated the activation of NF-kappaB. These results suggest that NPS 2143 could be potential agent for the treatment of inflammatory diseases including ALI. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Lee, Jae-Won AU - Lee JW AD - 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. FAU - Park, Hyun Ah AU - Park HA AD - 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; College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 305-764, Republic of Korea. FAU - Kwon, Ok-Kyoung AU - Kwon OK AD - 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, 99 Daehak-ro, Yuseong-gu, Daejeon, 305-764, Republic of Korea. FAU - Park, Ji-Won AU - Park JW AD - 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. FAU - Lee, Gilhye AU - Lee G AD - 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; School of Life Science and Biotechnology, Korea University, Seoul, Republic of Korea. FAU - Lee, Hee Jae AU - Lee HJ AD - Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Kangwon, 200-701, Republic of Korea. FAU - Lee, Seung Jin AU - Lee SJ AD - College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 305-764, Republic of Korea. FAU - Oh, Sei-Ryang AU - Oh SR AD - 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. FAU - Ahn, Kyung-Seop AU - Ahn KS AD - 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. Electronic address: ksahn@kribb.re.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170808 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (N-(2-hydroxy-3-(2-cyano-3-chlorophenoxy)propyl)-1,1-dimethyl-2-(2-nephthyl)ethylamine) RN - 0 (NF-kappa B) RN - 0 (Naphthalenes) RN - 0 (Receptors, Calcium-Sensing) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (interleukin-6, mouse) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.99.- (Ptgs2 protein, mouse) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 3.4.21.37 (Leukocyte Elastase) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Acute Lung Injury/chemically induced/*prevention & control MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Bronchoalveolar Lavage Fluid/chemistry MH - Cell Line MH - Chemokine CCL2/biosynthesis MH - Cyclooxygenase 2/biosynthesis MH - Enzyme Activation/drug effects MH - Epithelial Cells/drug effects MH - Humans MH - Interleukin-6/metabolism MH - Leukocyte Elastase/metabolism MH - Lipopolysaccharides MH - Lung/pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B/biosynthesis MH - Naphthalenes/*pharmacology MH - Nitric Oxide Synthase Type II/biosynthesis MH - Pneumonia/chemically induced/*prevention & control MH - Receptors, Calcium-Sensing/*antagonists & inhibitors MH - Respiratory Mucosa/cytology/*drug effects MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - ALI OT - MCP-1 OT - NF-kappaB OT - NPS 2143 OT - Neutrophils EDAT- 2017/08/12 06:00 MHDA- 2017/11/08 06:00 CRDT- 2017/08/12 06:00 PHST- 2017/02/06 00:00 [received] PHST- 2017/06/22 00:00 [revised] PHST- 2017/07/22 00:00 [accepted] PHST- 2017/08/12 06:00 [pubmed] PHST- 2017/11/08 06:00 [medline] PHST- 2017/08/12 06:00 [entrez] AID - S0161-5890(17)30442-X [pii] AID - 10.1016/j.molimm.2017.07.012 [doi] PST - ppublish SO - Mol Immunol. 2017 Oct;90:150-157. doi: 10.1016/j.molimm.2017.07.012. Epub 2017 Aug 8.