KN-62 enhances Chlamydia pneumoniae-induced p44/p42 mitogen-activated protein kinase activation in murine fibroblasts and attenuates in vitro infection

Chlamydia pneumoniae elementary bodies were demonstrated to increase the proliferation of murine fibroblast cell line L-929 and rapidly activate p44/p42 mitogen-activated protein kinase (MAPK) in a protein kinase C. (PKC) and protein kinase A (PKA)-independent way. Ca2+/calmodulin-dependent protein kinase (CaM kinase) inhibitor KN-62 significantly enhanced C. pneumoniae-induced MAPK phosphorylation, suggesting negative control of CaM kinase pathway on the MAPK cascade. In in vitro infection assay, the upstream MAPK kinase 1/2 inhibitor U0126 increased 2.5-fold C. pneumoniae infectivity in L-929 cells, while KN-62 reduced the infection by 36%. Our findings provide insight into the molecular mechanisms of bacterium-host cell interactions and demonstrate the protective role of MAPK in murine fibroblasts, suggesting novel therapeutic approaches to the treatment and prevention of chlamydial infections. (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.