PMID- 27676418
OWN - NLM
STAT- MEDLINE
DCOM- 20171128
LR  - 20201209
IS  - 1521-0499 (Electronic)
IS  - 0190-2148 (Linking)
VI  - 42
IP  - 7
DP  - 2016 Sep
TI  - Lack of matrix metalloproteinase 3 in mouse models of lung injury ameliorates the 
      pulmonary inflammatory response in female but not in male mice.
PG  - 365-379
AB  - BACKGROUND: The acute respiratory distress syndrome (ARDS) is a complex pulmonary 
      disorder in which the local release of cytokines and chemokines appears central 
      to the pathophysiology. OBJECTIVE: Based on the known role of matrix 
      metalloproteinase-3 (MMP3) in inflammatory processes, the objective was to 
      examine the role of MMP3 in the pathogenesis of ARDS through the modulation of 
      pulmonary inflammation. MATERIALS AND METHODS: Female and male, wild type 
      (MMP3(+/+)) and knock out (MMP3(-/-)) mice were exposed to two, clinically 
      relevant models of ARDS including (i) lipopolysaccharide (LPS)-induced lung 
      injury, and (ii) hydrochloric acid-induced lung injury. Parameters of lung injury 
      and inflammation were assessed through measurements in lung lavage including 
      total protein content, inflammatory cell influx, and concentrations of mediators 
      such as TNF-alpha, IL-6, G-CSF, CXCL1, CXCL2, and CCL2. Lung histology and compliance 
      were also evaluated in the LPS model of injury. RESULTS: Following intra-tracheal 
      LPS instillation, all mice developed lung injury, as measured by an increase in 
      lavage neutrophils, and decrease in lung compliance, with no overall effect of 
      genotype observed. Increased concentrations of lavage inflammatory cytokines and 
      chemokines were also observed following LPS injury, however, LPS-instilled female 
      MMP3(-/-) mice had lower levels of inflammatory mediators compared to 
      LPS-instilled female MMP3(+/+) mice. This effect of the genotype was not observed 
      in male mice. Similar findings, including the MMP3-related sex differences, were 
      also observed after acid-induced lung injury. CONCLUSION: MMP3 contributes to the 
      pathogenesis of ARDS, by affecting the pulmonary inflammatory response in female 
      mice in relevant models of lung injury.
FAU - Puntorieri, Valeria
AU  - Puntorieri V
AD  - a Department of Physiology and Pharmacology , Lawson Health Research Institute, 
      Western University , London , Ontario , Canada.
FAU - McCaig, Lynda A
AU  - McCaig LA
AD  - a Department of Physiology and Pharmacology , Lawson Health Research Institute, 
      Western University , London , Ontario , Canada.
FAU - Howlett, Christopher J
AU  - Howlett CJ
AD  - b Department of Pathology and Laboratory Medicine , Western University , London , 
      Ontario , Canada.
FAU - Yao, Li-Juan
AU  - Yao LJ
AD  - c Department of Medicine , Western University , London , Ontario , Canada.
FAU - Lewis, James F
AU  - Lewis JF
AD  - c Department of Medicine , Western University , London , Ontario , Canada.
FAU - Yamashita, Cory M
AU  - Yamashita CM
AD  - a Department of Physiology and Pharmacology , Lawson Health Research Institute, 
      Western University , London , Ontario , Canada.
AD  - c Department of Medicine , Western University , London , Ontario , Canada.
FAU - Veldhuizen, Ruud A W
AU  - Veldhuizen RA
AD  - a Department of Physiology and Pharmacology , Lawson Health Research Institute, 
      Western University , London , Ontario , Canada.
AD  - c Department of Medicine , Western University , London , Ontario , Canada.
LA  - eng
PT  - Journal Article
DEP - 20160927
PL  - England
TA  - Exp Lung Res
JT  - Experimental lung research
JID - 8004944
RN  - 0 (Lipopolysaccharides)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.17 (Mmp3 protein, mouse)
RN  - QTT17582CB (Hydrochloric Acid)
SB  - IM
MH  - Acute Lung Injury/chemically induced
MH  - Animals
MH  - Female
MH  - Humans
MH  - Hydrochloric Acid/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Matrix Metalloproteinase 3/genetics/*pharmacology
MH  - Mice
MH  - Pneumonia/*chemically induced
MH  - Respiratory Distress Syndrome/*etiology
MH  - Sex Factors
OTO - NOTNLM
OT  - acute respiratory distress syndrome
OT  - lung injury
OT  - matrix metalloproteinases
OT  - pulmonary inflammation
EDAT- 2016/10/25 06:00
MHDA- 2017/11/29 06:00
CRDT- 2016/09/28 06:00
PHST- 2016/10/25 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2016/09/28 06:00 [entrez]
AID - 10.1080/01902148.2016.1231243 [doi]
PST - ppublish
SO  - Exp Lung Res. 2016 Sep;42(7):365-379. doi: 10.1080/01902148.2016.1231243. Epub 
      2016 Sep 27.