title: Aldosterone up-regulates MMP-9 and MMP-9/NGAL expression in human neutrophils through p38, ERK1/2 and PI3K pathways.
abstract: Aldosterone and mineralocorticoid receptors are important regulators of inflammation. During this process, chemokines and extracellular matrix degradation by matrix metalloproteases, such as MMP-9, help leukocytes reaching swiftly and infiltrating the injured tissue, two processes essential for tissue repair. Leukocytes, such as neutrophils, are a rich source of MMP-9 and possess mineralocorticoid receptors (MR). The aim of our study was to investigate whether aldosterone was able to regulate proMMP-9, active MMP-9 and MMP-9/NGAL production in human neutrophils. Here we show that aldosterone increased MMP-9 mRNA in a dose- and time-dependent manner. This hormone up-regulated also dose-dependently proMMP-9 and active MMP-9 protein release as well as the MMP-9/NGAL protein complex. PI3K, p38 and ERK1/2 inhibition diminished these aldosterone-induced neutrophil productions. Furthermore, spironolactone, a MR antagonist, counteracted aldosterone-induced increases of proMMP-9, active MMP-9 and MMP-9/NGAL complex. These findings indicate that aldosterone could participate in tissue repair by modulating neutrophil activity and favoring extracellular matrix degradation.
authors.affiliation: (a)University of Lorraine, UMR_S U1116 (ex-U961 UHP-INSERM), Vandoeuvre-les-Nancy, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Gilet
authors.affiliation: (a)University of Lorraine, UMR_S U1116 (ex-U961 UHP-INSERM), Vandoeuvre-les-Nancy, France; Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan 430056, Hubei Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zou
authors.affiliation: (a)University of Lorraine, UMR_S U1116 (ex-U961 UHP-INSERM), Vandoeuvre-les-Nancy, France.
authors.forename: Meriem
authors.initials: M
authors.lastname: Boumenir
authors.affiliation: EA7300, Stress Immunity Pathogens Laboratory, Lorraine University, Vandoeuvre-les-Nancy, France.
authors.forename: Jean-Pol
authors.initials: JP
authors.lastname: Frippiat
authors.affiliation: (a)University of Lorraine, UMR_S U1116 (ex-U961 UHP-INSERM), Vandoeuvre-les-Nancy, France.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Thornton
authors.affiliation: (a)University of Lorraine, UMR_S U1116 (ex-U961 UHP-INSERM), Vandoeuvre-les-Nancy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lacolley
authors.affiliation: (a)University of Lorraine, UMR_S U1116 (ex-U961 UHP-INSERM), Vandoeuvre-les-Nancy, France; EA7300, Stress Immunity Pathogens Laboratory, Lorraine University, Vandoeuvre-les-Nancy, France. Electronic address: armelle.ropars@univ-lorraine.fr.
authors.forename: Armelle
authors.initials: A
authors.lastname: Ropars
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000450:Aldosterone / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018922:HL-60 Cells; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000450:Aldosterone; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Aldosterone; Inflammation; MAP kinases; MMP-9; NGAL; Neutrophil