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-α, (TNF-α) and interleukin-1β (IL-1β). Furthermore, carrageenan induced lung apoptosis (Bax and Bcl-2 expression) as well as nitrotyrosine formation, NF-κB 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.
TomlinsonAAppletonIMooreARGilroyDWWillisDMitchellJAWilloughbyDA. Cyclo-oxygenase and nitric oxide synthase isoforms in rat carrageenin-induced pleurisy. Br J Pharmacol1994; 113:693–8.
2.
NantelFDenisDGordonRNortheyACirinoMMettersKMChanCC. Distribution and regulation of cyclooxygenase-2 in carrageenan-induced inflammation. Br J Pharmacol1999; 128:853–9.
3.
SalveminiDWangZQWyattPSBourdonDMMarinoMHManningPTCurrieMG. Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. Br J Pharmacol1996; 118:829–38.
4.
CuzzocreaSNocentiniGDi PaolaR. Proinflammatory role of glucocorticoid-induced TNF receptor-related gene in acute lung inflammation. J Immunol2006; 177:631–41.
5.
FialkowLWangYDowneyGP. Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol Med2007; 42:153–64.
6.
ParekhABPennerR. Store depletion and calcium influx. Physiol Rev1997; 77:901–30.
7.
Perez-De La CruzVKonigsbergMPedraza-ChaverriJ. Cytoplasmic calcium mediates oxidative damage in an excitotoxic /energetic deficit synergic model in rats. Eur J Neurosci2008; 27: 1075–85.
8.
MorrisCJ. Carrageenan-induced paw edema in the rat and mouse. Methods Mol Biol2003; 225:115–21.
9.
WangMJJengKCKuoJSChenHLHuangHYChenWFLinSZ. c-Jun N-terminal kinase and, to a lesser extent, p38 mitogen-activated protein kinase regulate inducible nitric oxide synthase expression in hyaluronan fragments-stimulated BV-2 microglia. J Neuroimmunol2004; 146:50–62.
10.
XieZSmithCJVan EldikLJ. Activated glia induce neuron death via MAP kinase signaling pathways involving JNK and p38. Glia2004; 45:170–9.
11.
ZhangJZJingLGuoFYMaYWangYL. Inhibitory effect of ketamine on phosphorylation of the extracellular signal-regulated kinase 1/2 following brain ischemia and reperfusion in rats with hyperglycemia. Exp Toxicol Pathol2007; 59:227–35.
12.
CuzzocreaSMcDonaldMCFilipeHMCostantinoGMazzonESantagatiSCaputiAPThiemermannC. Effects of tempol, a membrane-permeable radical scavenger, in a rodent model of carrageenan-induced pleurisy. Eur J Pharmacol2000; 390:209–22.
13.
MinutoliLAntonuccioPRomeoC. Evidence for a role of mitogen-activated protein kinase 3/ mitogen-activated protein kinase in the development of testicular ischemia-reperfusion injury. Biol Reprod2005; 73:730–6.
14.
GenoveseTEspositoEMazzonEMuiaCDi PaolaRMeliRBramantiPCuzzocreaS. Evidence for the role of mitogen-activated protein kinase signaling pathways in the development of spinal cord injury. J Pharmacol Exp Ther2008; 325:100–14.
CuzzocreaSSautebinLDe SarroG. Role of IL-6 in the pleurisy and lung injury caused by carrageenan. J Immunol1999; 163:5094–104.
17.
CuzzocreaSRileyDPCaputiAPSalveminiD. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/ reperfusion injury. Pharm Rev2001; 53:135–59.
OhkawaHOhishiNYagiK. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem1979; 95:351–8.
20.
DavisRJ. The mitogen-activated protein kinase signal transduction pathway. J Biol Chem1993; 268: 14553–6.
21.
DuanWChanJHWongCHLeungBPWongWS. Anti-inflammatory effects of mitogen-activated protein kinase kinase inhibitor U0126 in an asthma mouse model. J Immunol2004; 172:7053–9.
22.
LeePJZhangXShanP. ERKl/2 mitogen-activated protein kinase selectively mediates IL-13-induced lung inflammation and remodeling in vivo. J Clin Invest2006; 116:163–73.
23.
CuzzocreaSCrisafulliCMazzonEEspositoEMuiaCAbdelrahmanMDi PaolaRThiemermannC. Inhibition of glycogen synthase kinase-3beta attenuates the development of carrageenan-induced lung injury in mice. Br J Pharmacol2006; 149:687–702.
24.
BowieAO'NeillLA. Oxidative stress and nuclear factor-kappaB activation: a reassessment of the evidence in the light of recent discoveries. Biochem Pharmacol2000; 59:13–23.
WooleyPHWhalenJDChapmanDLBergerAERichardKAAsparDGStaiteND. The effect of an interleukin-1 receptor antagonist protein on type II collagen-induced arthritis and antigen-induced arthritis in mice. Arthritis Rheum1993; 36:1305–14.
27.
MukherjeePYangSYWuBSongZMyersLKRobbinsPDWooleyPH. Tumour necrosis factor receptor gene therapy affects cellular immune responses in collagen induced arthritis in mice. Ann Rheum Dis2005; 64:1550–6.
28.
CuzzocreaSThiemermannCSalveminiD. Potential therapeutic effect of antioxidant therapy in shock and inflammation. Curr Med Chem2004; 11: 1147–62.
29.
BeckmanJS. Oxidative damage and tyrosine nitration from peroxynitrite. Chem Res Toxicol1996; 9:836–44.
30.
EiserichJPHristovaMCrossCE. Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature1998; 391: 393–7.
31.
ViragL. Poly(ADP-ribosyl)ation in asthma and other lung diseases. Pharmacol Res2005; 52:83–92.
32.
MerrillJEIgnarroLJShermanMPMelinekJLaneTE. Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J Immunol1993; 151:2132–41.
