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Tuomas Paimela, Juha M. Hyttinen, Johanna Viiri, Tuomas Ryhanen, Antero Salminen, Kai Kaarniranta; Celastrol Regulates Innate Immunity Response Via Nf-B And Hsp70 In Human Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):864.
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Elevated NF-ΚB activity and IL-6 secretion participates in the pathology of several age and inflammatory-related diseases, including age-related macular degeneration (AMD), in which retinal pigment epithelial cells are the key target. Recent findings indicate that heat shock protein 70 (Hsp70) may affect to the regulation of NF-ΚB. In the current study, by using celastrol, a novel anti-inflammatory compound, the effect of Hsp70 expression on NF-ΚB RelA/p65 activity were evaluated in human retinal pigment epithelial cells (ARPE-19).
The anti-inflammatory properties of celastrol were analysed by measuring interleukin-6 (IL-6) expression and endogenous NF-ΚB levels during lipopolysaccharide (LPS) exposure by using ELISAs. Cell viability was measured by MTT assay. Hsp70 expression levels were analysed by western blotting. The attenuation of Hsp70 expression was conducted by transfecting ARPE-19 cells with hsp70 small interfering RNA (siRNA). The activity of NF-ΚB RelA/p65 was measured using NF-ΚB consensus bound ELISAs.
Simultaneous exposures to LPS and celastrol reduced the IL-6 and endogenous NF-ΚB expression levels in ARPE-19 cells when compared to LPS exposure alone. In addition, the inhibition of NF-ΚB RelA/p65 activity by celastrol was attenuated when Hsp70 response was silenced by siRNA. The favourable anti-inflammatory concentrations of celastrol showed no signs of cytotoxic response.
Our findings reveal that celastrol is a novel plant compound which suppresses innate immunity response in human retinal pigment epithelial cells via NF-ΚB and Hsp70 regulation, and that Hsp70 is a critical regulator of NF-ΚB.
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