Involvement of c-Jun N-terminal kinase in rF1 mediated activation of murine peritoneal macrophages in vitro

Fraction 1 (F1) protein forms a capsule on the surface of Yersinia pestis. Recently, we reported rF1-induced activation of macrophages. In current investigation, we studied the role of JNK MAPK signal transduction pathway in rF1-induced activation of macrophages in vitro. SP600125, a specific inhibitor of JNK, inhibited JNK MAPK phosphorylation, indicating the specificity of the above response. Though, the rF1-induced phosphorylation of INK MAPK was also inhibited by upstream protein kinase C inhibitor H7, tyrosine kinase inhibitor genestein and PI3-K inhibitor wotmannin. Activation of the transcription factor NF-kB (phosphorylation of IkB) and c-Jun was observed in response to rF1 treatment. The rF1-induced JNK MAPK activity was correlated to the functional activation of macrophages by demonstrating the inhibition of NO, TNF-alpha production and microtubule polymerization caused by SP600125. Taken together, the data suggests the involvement of JNK MAPK/NF-kB pathway in rF1-induced activation of macrophages.