Figure 1.

The effect of MEK1/2 inhibition on malaria parasite growth and malaria-induced activation of MAPK signaling. A, effect of PD on P. falciparum growth as assessed by a SYBR Green assay. Shown are the data from a representative of four independent experiments, each performed in triplicate. Chloroquine, which can completely inhibit the parasite growth, was used as a control. B, the effect of PD on PbA growth was assessed by culturing blood cells from infected mice in the presence of PD. Untreated and chloroquine-treated parasites were used as controls. Shown are photographs under light microscopy of Giemsa-stained smears of cells. C and D, PbA-infected mice were injected i.p. with 3 mg of PD/kg body weight or vehicle daily starting at 6 h pi. Separately, PbA-infected mice were treated orally with either vehicle or 5 mg of trametinib/kg body weight daily starting at 6 h postinfection. At the indicated time points, spleens of mice (n = 2/group) were analyzed for MAPK activation and for c-Jun and c-Fos expression by Western blotting (C). The protein bands on blots were quantified by densitometry measurements and plotted (D). Shown are the results of a representative of two independent experiments. UI, uninfected mice; PbA, vehicle-treated infected mice (control); PbA-PD, PD-treated infected mice; PbA-T, trametinib-treated infected mice. Error bars, S.D.