Pathogenic Yersinia requires c-KIT activity for suppression of transcription factor and pro-inflammatory cytokine expression. (A-B) Analysis of signal transduction pathways in Y. pestis-infected THP1 cells in absence of c-KIT. THP1 cells untreated or pre-treated with 1μM OSI-930 for 18 h were infected with Y. pestis Ind195 at MOI 20 for 1h. RNA was isolated, converted to cDNA, and applied to a RT Profiler PCR Array for human signal transduction pathway expression analysis. Dot plots compare gene expression profiles between uninfected THP-1 cells and (A) Y. pestis Ind195-infected THP-1 cells or (B) OSI-930-pretreated, Y. pestis Ind195 infected THP-1 cells. Genes that do not exhibit significant expression changes between the control and experimental samples are concentrated between the two black lines. The black lines define the assay cut-off of 3-fold induction or 70% reduction of transcript levels. Genes of interest are highlighted in black. (C) Inhibition of c-KIT recovers EGR1, chemokine, and cell adhesion transcript levels in pathogenic Yersinia-infected THP1 cells. THP1 cells were pre-treated with 1μM OSI-930 for 18 h or were left untreated prior to infection with Y. pestis Ind195 at MOI 10 for 1 h. EGR1, VCAM1, CCL20, and IL-8 mRNA levels were determined by Taqman qPCR using total RNA isolated 24 h post-infection. Depicted RNA levels are relative to untreated THP1 control samples and were calculated using the 2-ΔΔCt formula. A ‘*” denotes that relative RNA levels were significantly different (p<0.05) compared to infected cells untreated with OSI930. Data is shown from three independent infection experiments performed in duplicate.