A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1

Cheung, Benny KW; Yim, Howard CH; Lee, Norris CM; Lau, Allan SY

It has been shown that inhibition of p38 MAPK either by specific inhibitor or siRNA reduced the expression of MKP-1 in LPS-or peptidoglycan-treated macrophages [14] . To determine the mechanisms involved in the BCGinduced MKP-1 expression, PBMo were pretreated with several inhibitors including PD98059 (inhibitor for MAP kinase kinase [MEK] or ERK1/2), SB203580 (inhibitor for p38 MAPK), SP600125 (inhibitor for JNK), and CAPE (inhibitor for NF-κB) for 1 hour. A range of concentrations of each inhibitor was used to test their optimal concentrations and effects on cell viability and kinase inhibitions. BCG was added afterwards and total RNA was harvested. The results demonstrated that, with the inhibition of ERK1/2 and p38 MAPK activities by their corresponding relatively specific inhibitors, MKP-1 expressions were significantly reduced ( Figure 3 ). In addition, using higher dose of SB203580, we showed that the inhibition is increased further (data not shown). On the contrary, pretreatment of the cells with CAPE and SP600125 did not affect the induction of MKP-1 by BCG ( Figure 3 ). These results suggest that BCG-induced MKP-1 expression is dependent on both p38 MAPK and ERK1/2.