PMID- 16897233 OWN - NLM STAT- MEDLINE DCOM- 20061222 LR - 20181113 IS - 0913-8668 (Print) IS - 0913-8668 (Linking) VI - 20 IP - 3 DP - 2006 TI - Effects of sivelestat, a new elastase inhibitor, on IL-8 and MCP-1 production from stimulated human alveolar epithelial type II cells. PG - 159-65 AB - PURPOSE: The alveolar epithelial cell type II (AEC-II) is itself able to amplify lung inflammation by producing inflammatory cytokines and chemokines, leading to the activation and recruitment of phagocytes. Sivelestat, a new neutrophil elastase inhibitor, has been shown to attenuate acute lung injury in animal experiments. In the current study, we assessed the effects of sivelestat on the production of chemokines from cultured A549 cells, a human AEC-II-like cell line. METHODS: A549 cells were stimulated with endotoxin or tumor necrosis factor-alpha in the presence of sivelestat (1-100 microg x ml(-1)). Culture supernatant levels of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were determined by enzyme-linked immunosorbent assay. The expression of IL-8 and MCP-1 mRNAs in stimulated A549 cells in the presence of sivelestat (100 microg x ml(-1)) was quantified by real-time polymerase chain reaction. RESULTS: Sivelestat, at 100 microg x ml(-1) reduced the accumulation of IL-8 and MCP-1 in the culture medium. The high dose of sivelestat significantly inhibited the expression of IL-8 mRNA in A549 cells. The drug also decreased MCP-1 mRNA expression, although not significantly. CONCLUSION: These data suggest that a high dose of sivelestat regulates the production of IL-8 and MCP-1 in AEC-II. FAU - Misumi, Takuyo AU - Misumi T AD - Department of Anesthesia and Perioperative Medicine, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Kobe 650-0017, Japan. FAU - Tanaka, Takanori AU - Tanaka T FAU - Mikawa, Katsuya AU - Mikawa K FAU - Nishina, Kahoru AU - Nishina K FAU - Morikawa, Osamu AU - Morikawa O FAU - Obara, Hidefumi AU - Obara H LA - eng PT - Journal Article PL - Japan TA - J Anesth JT - Journal of anesthesia JID - 8905667 RN - 0 (Chemokine CCL2) RN - 0 (Endotoxins) RN - 0 (Interleukin-8) RN - 0 (RNA, Messenger) RN - 0 (Serine Proteinase Inhibitors) RN - 0 (Sulfonamides) RN - 0 (Tumor Necrosis Factor-alpha) RN - DWI62G0P59 (sivelestat) RN - TE7660XO1C (Glycine) SB - IM MH - Cells, Cultured/drug effects/immunology/metabolism MH - Chemokine CCL2/*biosynthesis/drug effects/immunology MH - Dose-Response Relationship, Drug MH - Endotoxins/administration & dosage MH - Enzyme-Linked Immunosorbent Assay MH - Epithelial Cells/*drug effects/immunology/metabolism MH - Glycine/*analogs & derivatives/pharmacology MH - Humans MH - In Vitro Techniques MH - Interleukin-8/*biosynthesis/immunology MH - Polymerase Chain Reaction/methods MH - Pulmonary Alveoli/*drug effects/immunology/metabolism MH - RNA, Messenger/immunology MH - Respiratory Mucosa/drug effects/immunology MH - Serine Proteinase Inhibitors/*pharmacology MH - Sulfonamides/*pharmacology MH - Time Factors MH - Tumor Necrosis Factor-alpha/administration & dosage EDAT- 2006/08/10 09:00 MHDA- 2006/12/23 09:00 CRDT- 2006/08/10 09:00 PHST- 2005/03/28 00:00 [received] PHST- 2006/01/29 00:00 [accepted] PHST- 2006/08/10 09:00 [pubmed] PHST- 2006/12/23 09:00 [medline] PHST- 2006/08/10 09:00 [entrez] AID - 10.1007/s00540-006-0391-z [doi] PST - ppublish SO - J Anesth. 2006;20(3):159-65. doi: 10.1007/s00540-006-0391-z.