Effect of PD98059, a selective MAPK3/MAPK1 inhibitor, on acute lung injury in mice.
The aim of the present study is to evaluate the contribution of mitogen-activated protein kinase 1-3 MAPK3/MAPK1) in a model of acute lung inflammation in mice. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs) in the pleural cavity, infiltration of PMNs in lung tissues and subsequent adhesion molecule expression (I-CAM and P-selectin), lipid peroxidation, and increased production of tumour necrosis factor-alpha, (TNF-alpha) and interleukin-1beta (IL-1beta). Furthermore, carrageenan induced lung apoptosis (Bax and Bcl-2 expression) as well as nitrotyrosine formation, NF-kB activation, and pJNK expression, as determined by immunohistochemical analysis of lung tissues and the degree of lung inflammation and tissue injury (histological score). Administration of PD98059, an inhibitor of MAPK3/MAPK1 (10 mg/kg) 1 h after carrageenan caused a reduction in all the parameters of inflammation measured. Thus, based on these findings we propose that inhibitors of the MAPK3/MAPK1 signaling pathways, such as PD98059, may be useful in the treatment of various inflammatory diseases.
Di Paola
R
R
IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy.
Crisafulli
C
C
Mazzon
E
E
Genovese
T
T
Paterniti
I
I
Bramanti
P
P
Cuzzocrea
S
S
D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002351:Carrageenan; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D010766:Phosphorylation; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; C494827:Bax protein, mouse; D016207:Cytokines; D005419:Flavonoids; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; C000606205:Nfkbia protein, mouse; D019007:P-Selectin; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D051028:bcl-2-Associated X Protein; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one