Leukotactin(Lkn)-1 is a CC chemokine and is upregulated inmacrophages in response to Mycobacterium tuberculosis (MTB)infection. We investigated whether mitogen-activated proteinkinases (MAPKs) are involved in MTB-induced expression ofLkn-1. The up-regulation of Lkn-1 by infection with MTB wasinhibited in cells treated with inhibitors specific for JNK(SP600125) or p38 MAPK (SB202190). Since the up-regulation ofLkn-1 by MTB has been reported to be mediated by thePI3-K/PDK1/Akt signaling, we examined whether JNK and/orp38 MAPK are also involved in this signal pathway.MTB-induced Akt phosphorylation was blocked by treatmentwith JNK- or p38 MAPK-specific inhibitors implying that p38 andJNK are upstream of Akt. In addition, treatment with thePI3-K-specific inhibitor inhibited MTB-stimulated activation ofJNK or p38 MAPK implying that PI3-K is upstream of JNK andp38 MAPK. These results collectively suggest that JNK and p38MAPK are involved in the signal pathway responsible forMTB-induced up-regulation of Lkn-1.