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Figure 1: Altered signaling mechanisms contributing to asthmatic airway smooth muscle cell phenotype. Studies in our laboratory revealed some important changes in the HASM cells from asthmatic donors compared to the cells from nonasthmatic donors, suggesting a potential role for these mechanisms in the asthmatic phenotype of ASM cells. (a) Inflammatory cytokine TNF-α (10 ng/mL) induced differentially elevated CD38 expression in asthmatic HASM cells compared to the nonasthmatic HASM cells, as early as 6 hrs following addition of the cytokine ( /nonasthmatic or asthmatic HASM cells, * , significantly different from the vehicle-treated controls; ** , significantly different from the nonasthmatic HASM cells treated with TNF-α). (b) In HASM cells from asthmatic donors, TNF-α (10 ng/mL, 24 hrs of exposure) caused significant attenuation of miR-140-3p expression compared to the nonasthmatic HASM cells. The basal miR-140-3p expression levels were comparable between nonasthmatic and asthmatic HASM cells ( /nonasthmatic group; /asthmatic group, * , significantly different from the nonasthmatic group). (c–e) (Left and right panels) HASM cells obtained from asthmatic donors showed elevated basal and TNF-α-induced activations of ERK and p38 MAP kinases compared to the nonasthmatic HASM cells. TNF-α-induced JNK MAP Kinase activation was attenuated in asthmatic HASM cells compared to the nonasthmatic cells (blots representative of 5 independent experiments). (a) and (c–e) are reproduced with permission from [12]. Panel (b) is Reproduced with permission from [28]. Altered signaling mechanisms contributing to asthmatic airway smooth muscle cell phenotype.