Far infrared therapy inhibits vascular endothelial inflammation via the induction of heme oxygenase-1

Abstract

Objective: Survival of arteriovenous fistulas (AVFs) in hemodialysis patients is associated with both far infrared (FIR) therapy and length polymorphisms of the heme oxygenase-1 (HO-1) promoter. In this study, we evaluated whether there is an interaction between FIR radiation and HO-1 in regulating vascular inflammation.

Methods and results: Treatment of cultured human umbilical vein endothelial cells (ECs) with FIR radiation stimulated HO-1 protein, mRNA, and promoter activity. HO-1 induction was dependent on the activation of the antioxidant responsive element/NF-E2-related factor-2 complex, and was likely a consequence of heat stress. FIR radiation also inhibited tumor necrosis factor (TNF)-alpha-mediated expression of E-selectin, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte chemoattractant protein-1, interleukin-8, and the cytokine-mediated adhesion of monocytes to ECs. The antiinflammatory action of FIR was mimicked by bilirubin, and was reversed by the HO inhibitor, tin protoporphyrin-IX, or by the selective knockdown of HO-1. Finally, the antiinflammatory effect of FIR was also observed in patients undergoing hemodialysis.

Conclusions: These results demonstrate that FIR therapy exerts a potent antiinflammatory effect via the induction of HO-1. The ability of FIR therapy to inhibit inflammation may play a critical role in preserving blood flow and patency of AVFs in hemodialysis patients.

Figures

Figure 1

FIR radiation for 40 minutes stimulates HO-1 protein (A) and mRNA (C) expression in HUVEC. Duration-dependent effect of FIR radiation on HO-1 protein (B) and mRNA (D) expression in HUVEC six hours after FIR exposure. Results are means ± SD (n=3-5). *Statistically significant effect of FIR therapy.

Figure 2

FIR radiation for 40 minutes stimulates HO-1 promoter activity in HUVEC six hours after FIR exposure (A). FIR radiation for 40 minutes stimulates Nrf2 protein expression (B). Duration-dependent effect of FIR radiation on Nrf2 protein expression (C). Results are means ± SD (n=3-6). *Statistically significant effect of FIR therapy.

Figure 3

FIR radiation for 40 minutes inhibits TNFα (100ng/ml)-stimulated adhesion receptor expression in HUVEC (A). Duration-dependent effect of FIR radiation on adhesion receptor expression (B). FIR radiation inhibits TNFα (100ng/ml for 6 hours)-stimulated MCP-1 (C) and IL-8 (D) production. Results are means ± SD (n=3-4). *Statistically significant effect of FIR radiation.

Figure 4

Monocyte adhesion (A, C) and HO-1 protein (B) in HUVEC treated with HO-1 or NT siRNA, FIR radiation, or untreated HUVEC exposed to TNFα in the presence of SnPP, BR, CO, or Fe. Results ar means ± SD (n=3-6). *Statistically significant effect versus untreated cells. †Statistically significant effect of BR.