PMID- 27355745 OWN - NLM STAT- MEDLINE DCOM- 20170330 LR - 20170330 IS - 1678-2674 (Electronic) IS - 0102-8650 (Linking) VI - 31 IP - 6 DP - 2016 Jun TI - Neutrophil elastase ameliorates matrix metalloproteinase-9 to promote lipopolysaccharide-induced acute lung injury in mice 1. PG - 382-8 LID - S0102-86502016000600382 [pii] LID - 10.1590/S0102-865020160060000004 [doi] AB - PURPOSE: To investigate the regulatory roles of neutrophil elastase (NE) and matrix metalloproteinase-9 (MMP-9) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. METHODS: To construct LPS-induced ALI mouse models, wild-type C57BL/6 mice were administered 5.0 mg/kg of LPS through endotracheal, and/or 1.0 mg/kg of ONO-5046, and/or 20.0 mg/kg of chemically modified tetracycline-3 (CMT-3) by gavage. The levels of MMP-9, tissue inhibitor of metalloprotease-1, interleukin (IL)-6 were detected by real time RT-PCR at 6 h, 24 h and 48 h, and tumor necrosis factor (TNF), lung wet-dry weight ratio, white blood cell (WBC) count and polymorphonuclear (PMN) count in bronchoalveolar lavage fluid (BALF) were tested at 48 h after administration. The 5-day survival analysis of the ALI mice was also performed. RESULTS: Both ONO-5046 and CMT-3, regardless of being used individually or combined, significantly reduced the levels of MMP-9, IL-6, and TNF in lung tissue as well as in BALF, and the WBC and PMN count in BALF. Combined treatment with ONO-5046 and CMT-3 remarkably improved the survival rate of ALI mice. CONCLUSION: Neutrophil elastase synergizes with matrix metalloproteinase-9 to promote and regulate the release of inflammatory mediators and the infiltration of inflammatory cells, consequently affecting the survival of lipopolysaccharide-induced acute lung injury mice. FAU - Guo, Yingfei AU - Guo Y AD - Department of Emergency, General Hospital of PLA, Beijing, China. Design the protocol, acquisition and analysis of data, technical procedures, manuscript writing, final approved. AD - Department of Emergency or Respiration, First Affiliated, General Hospital of PLA, Beijing, China. Statistical analysis, technical procedures, final approved the manuscript. FAU - Ma, Lingyun AU - Ma L AD - Department of Emergency, General Hospital of PLA, Beijing, China. Design the protocol, acquisition and analysis of data, technical procedures, manuscript writing, final approved. AD - Department of Emergency or Respiration, First Affiliated, General Hospital of PLA, Beijing, China. Statistical analysis, technical procedures, final approved the manuscript. FAU - Zhang, Fei AU - Zhang F AD - Department of Emergency, General Hospital of PLA, Beijing, China. Design the protocol, acquisition and analysis of data, technical procedures, manuscript writing, final approved. FAU - Sun, Rongju AU - Sun R AD - Department of Emergency, General Hospital of PLA, Beijing, China. Design the protocol, acquisition and analysis of data, technical procedures, manuscript writing, final approved. FAU - Li, Tanshi AU - Li T AD - Department of Emergency, General Hospital of PLA, Beijing, China. Design the protocol, acquisition and analysis of data, technical procedures, manuscript writing, final approved. LA - eng PT - Journal Article PL - Brazil TA - Acta Cir Bras JT - Acta cirurgica brasileira JID - 9103983 RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Sulfonamides) RN - 0 (Tetracyclines) RN - 0 (Timp1 protein, mouse) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 0 (Tumor Necrosis Factors) RN - 0 (interleukin-6, mouse) RN - 0 (tetracycline CMT-3) RN - DWI62G0P59 (sivelestat) RN - EC 3.4.21.37 (Leukocyte Elastase) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - TE7660XO1C (Glycine) SB - IM MH - Acute Lung Injury/blood/chemically induced/*enzymology MH - Animals MH - Bronchoalveolar Lavage Fluid/cytology MH - Disease Models, Animal MH - Glycine/administration & dosage/*analogs & derivatives MH - Inflammation Mediators/metabolism MH - Interleukin-6/metabolism MH - Leukocyte Count MH - Leukocyte Elastase/drug effects/*metabolism MH - Lipopolysaccharides MH - Matrix Metalloproteinase 9/analysis/drug effects/*metabolism MH - Mice, Inbred C57BL MH - Neutrophils MH - Sulfonamides/*administration & dosage MH - Survival Analysis MH - Tetracyclines/*administration & dosage MH - Time Factors MH - Tissue Inhibitor of Metalloproteinase-1/metabolism MH - Tumor Necrosis Factors/metabolism EDAT- 2016/06/30 06:00 MHDA- 2017/03/31 06:00 CRDT- 2016/06/30 06:00 PHST- 2016/02/24 00:00 [received] PHST- 2016/05/23 00:00 [accepted] PHST- 2016/06/30 06:00 [entrez] PHST- 2016/06/30 06:00 [pubmed] PHST- 2017/03/31 06:00 [medline] AID - S0102-86502016000600382 [pii] AID - 10.1590/S0102-865020160060000004 [doi] PST - ppublish SO - Acta Cir Bras. 2016 Jun;31(6):382-8. doi: 10.1590/S0102-865020160060000004.