FIG. 9.

SOD3-transduced MSCs inhibit TLR-7 activation, NF-κB expression, MAP kinase, JAK-STAT signaling, and late-phase responses independent of TLR-7 activation. (A) Tissue extracts from mouse back skins were prepared and blotted to evaluate TLR-7 and NF-κB expression. (B–D) Phosphorylated STAT1, STAT3, JAK1, JAK2, JNK, and p38 levels were determined from mouse back skins. Western blot analysis was performed with antibodies specific for the molecules indicated. (E) The expression of adenosine receptors AR-A1, AR-A2A, AR-A2B, and AR-A3 mRNAs at days 6 and 12 in normal and IMQ-induced psoriatic mice skins was assessed by RT-PCR. GAPDH was used as a control. (F) The cAMP concentrations in tissue and blood plasma were measured by a cAMP ELISA kit (Enzo Life Sciences). (G) Phosphorylation of PKA substrate and CREB in control versus IMQ-induced psoriatic mice either treated with IMQ alone or SOD3-transduced MSCs. The numerical values on the blot represent % relative DU, as measured by ImageJ software (National Institutes of Health). Control group was set as 100% DU in each regimen. (H) Regulation of PDE4A and PDE4B mRNA expression by MSCs or SOD3-transduced MSCs in IMQ-induced psoriatic mouse models. Error bar indicates SD; ^#p < 0.05, ^##p < 0.01, ^###p < 0.001 (control group vs. IMQ-treated group for all cases); *p < 0.05, **p < 0.01, ***p < 0.001 (IMQ-treated group vs. SOD3-transduced MSCs or MSC-treated group). cAMP, cyclic adenosine monophosphate; CREB, cAMP response element-binding protein; DU, densitometric unit; JAK-STAT, Janus kinase-signal transducer and activator of transcription; MAP, mitogen-activated protein; NF-κB, nuclear factor-kappa B; PDE4, phosphodiesterase 4; RT, reverse transcriptase; TLR-7, toll-like receptor-7.