Phosphorylation of p42/44 MAP kinase is required for rF1-induced activation of murine peritoneal macrophages.
The Fraction 1 (F1) antigen of Yersinia pestis is known to induce thymocyte proliferation. It serves as a major protective antigen against challenge of Y. pestis. Recently, we reported rF1-induced activation of macrophages. Current investigation elucidates the role of p42/44 mitogen-activated protein kinases (MAPK)-mediated signal transduction in murine peritoneal macrophages on stimulation with rF1 (10 microg/ml) in vitro. The p42/44 MAPK activation was determined by studying the expression of the phosphorylated p42/44 MAPK in rF1-treated macrophages. PD98059, a specific inhibitor of MAPK kinase (MEK) inhibited the p42/44 MAPK phosphorylation, indicating the specificity of the above response. Furthermore, the rF1-induced phosphorylation of p42/44 MAPK is found to blocked by upstream protein kinase C inhibitor H7, tyrosine kinase inhibitor genistein and phosphoinositol-3-kinase (PI3-K) inhibitor wortmannin. Additionally, phosphorylation of JNK and activation of the transcription factor, c-jun and c-fos was also observed in response to rF1 treatment. The rF1-induced activation of p42/44 MAPK was correlated to the functional activation of macrophages by demonstrating the inhibition of actin rearrangement, IL-1, TNF-alpha and NO production caused by PD98059 in the rF1-treated macrophages.
Sharma
Rajesh Kumar
RK
School of Biotechnology, Faculty of Science, Banaras Hindu University, Varanasi-221 005, Uttar Pradesh, India.
Sodhi
Ajit
A
Batra
Harsh Vardhan
HV
Tuteja
Urmil
U
D000199:Actins / Q000378:metabolism; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D015010:Yersinia pestis / Q000276:immunology / Q000472:pathogenicity
D000199:Actins; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D005419:Flavonoids; D007375:Interleukin-1; D016760:Proto-Oncogene Proteins c-fos; D009569:Nitric Oxide; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one