Mild electrical stimulation with heat shock reduces inflammatory symptoms in the imiquimod‐induced psoriasis mouse model

Abstract

Psoriasis is a chronic skin disease caused by immune disorder. The chronic skin inflammation involves inflammatory molecules that are released from T lymphocytes and keratinocytes. Therefore, developing an anti-inflammatory therapy that is suitable for long-term treatment is needed. Electrical stimulation induces biological responses by modulating intracellular signaling pathways. Our previous studies showed that the optimized combination treatment of mild electrical stimulation (MES, 0.1-millisecond; ms, 55-pulses per second; pps) and heat shock (HS, 42°C) modulates inflammatory symptoms of metabolic disorders and chronic kidney disease in mice models and clinical trials. Here, we investigated the effect of MES+HS treatment on imiquimod-induced psoriasis mouse model. Topical application of imiquimod cream (15 mg) to mice ear induced keratinocyte hyperproliferation and psoriasis-like inflammation. In MES+HS-treated mice, imiquimod-induced skin hyperplasia was significantly decreased. MES+HS treatment reduced the protein expression of IL-17A and the infiltration of CD3-positive cells in lesioned skin. In addition, MES+HS-treated mice had decreased mRNA expression level of antimicrobial molecules (S100A8 and Reg3γ) which aggravate psoriasis. In IL-17A-stimulated HaCaT cells, MES+HS treatment significantly lowered the mRNA expression of aggravation markers (S100A8, S100A9 and β-defensin2). Taken together, our study suggested that MES+HS treatment improves the pathology of psoriasis via decreasing the expression of inflammatory molecules.

Mild electrical stimulation with heat shock attenuates renal pathology in adriamycin-induced nephrotic syndrome mouse model

“…Simultaneous HS treatment was applied at a temperature of 42 °C. These treatment conditions have been optimized and reported in our previous studies 17 , 19 , 23 . The mice in the control and ADR groups were placed in the above chamber for 10 min without MES + HS treatment.…”

“…To determine the protein expression level, whole kidney samples and MPC5 cells were lysed in lysis buffer (25 nmol/mL HEPES, 10 mmol/mL Na 4 P 2 O 7 ∙10H 2 O, 100 mmol/mL NaF, 5 mmol/mL EDTA, 2 mmol/mL Na 3 VO 4 , 1% Triton X-100) and protein lysates were subjected to SDS-PAGE and Western blot analysis as described previously 19 . Anti-phospho-Akt (#9271), anti-Akt (#9272), anti-phospho-BAD (#4366), anti-BAD (#9239) and anti-Cleaved caspase 3 (#9661) antibodies from Cell Signaling Technology were used for antibody reaction.…”

“…After differentiation, MPC5 cells were incubated with 200 nmol/mL of adriamycin (ADR, Sigma-Aldrich Co. LLC, USA) and treated with MES + HS. MES + HS treatment was performed as described previously 17 , 19 , 23 . Briefly, MPC5 cells were plated on 35-mm culture dishes and treated with MES + HS for 10 min.…”

“…Particularly, it has been shown that electrical stimulation influences cellular migration and wound healing via activating phosphatidylinositol 3-OH kinase (PI3K)-Akt pathway 16 . Our previous works on mild electrical stimulation (MES) with heat shock (HS) have revealed that this combination treatment is effective in several disease models 17 – 19 . Moreover, we have investigated the biological effects of optimized MES + HS treatment and elucidated some of the mechanistic pathways responsible for the effectiveness of MES + HS.…”

“…Moreover, we have investigated the biological effects of optimized MES + HS treatment and elucidated some of the mechanistic pathways responsible for the effectiveness of MES + HS. Using murine models, we have previously shown that MES + HS ameliorated the pathologies in type 2 diabetes mellitus (T2DM), obesity, hepatic ischemia reperfusion injury, and skin psoriasis 17 – 19 . In clinical investigations, we have reported that MES + HS improved insulin resistance, glucose metabolism parameters and inflammatory parameters in T2DM patients without adverse effects, pointing to the safety of MES + HS 20 – 22 .…”