Abstract
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.
MeSH terms
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Acute Lung Injury / chemically induced
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Acute Lung Injury / drug therapy*
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Acute Lung Injury / enzymology
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Acute Lung Injury / immunology
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Acute Lung Injury / pathology
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Animals
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Anti-Inflammatory Agents / pharmacology*
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Apoptosis / drug effects
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Carrageenan
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Cytokines / metabolism
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Disease Models, Animal
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Flavonoids / pharmacology*
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I-kappa B Proteins / metabolism
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Inflammation Mediators / metabolism
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Intercellular Adhesion Molecule-1 / metabolism
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Lipid Peroxidation / drug effects
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Lung / drug effects*
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Lung / enzymology
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Lung / immunology
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Lung / pathology
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Male
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Mice
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 3 / metabolism
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NF-KappaB Inhibitor alpha
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / metabolism
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P-Selectin / metabolism
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Phosphorylation
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Pleurisy / chemically induced
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Pleurisy / drug therapy*
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Pleurisy / enzymology
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Pleurisy / immunology
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Pleurisy / pathology
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Protein Kinase Inhibitors / pharmacology*
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Signal Transduction / drug effects
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Transcription Factor RelA / metabolism
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Tyrosine / analogs & derivatives
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Tyrosine / metabolism
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bcl-2-Associated X Protein / metabolism
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Anti-Inflammatory Agents
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Bax protein, mouse
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Cytokines
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Flavonoids
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I-kappa B Proteins
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Inflammation Mediators
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Nfkbia protein, mouse
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P-Selectin
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins c-bcl-2
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Rela protein, mouse
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Transcription Factor RelA
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bcl-2-Associated X Protein
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Intercellular Adhesion Molecule-1
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NF-KappaB Inhibitor alpha
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Nitric Oxide
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3-nitrotyrosine
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Tyrosine
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Carrageenan
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Mapk1 protein, mouse
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one