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Celastrol regulates innate immunity response via NF-κB and Hsp70 in human retinal pigment epithelial cells.
Celastrol regulates innate immunity response via NF-κB and Hsp70 in human retinal pigment epithelial cells.
- Source :
-
Pharmacological research [Pharmacol Res] 2011 Nov; Vol. 64 (5), pp. 501-8. Date of Electronic Publication: 2011 Jun 07. - Publication Year :
- 2011
-
Abstract
- Elevated nuclear factor kappa B (NF-κB) activity and interleukin-6 (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 reveal that heat shock protein 70 (Hsp70) may affect regulation of NF-κB. In the current study, effects of Hsp70 expression on NF-κB RelA/p65 activity were evaluated in human retinal pigment epithelial cells (ARPE-19) by using celastrol, a novel anti-inflammatory compound. Anti-inflammatory properties of celastrol were determined by measuring expression levels of IL-6 and endogenous NF-κB levels during lipopolysaccharide (LPS) exposure by using enzyme-linked immunosorbent assays (ELISA). Cell viability was measured by MTT and LDH assay, and Hsp70 expression levels were analyzed by Western blotting. ARPE-19 cells were transfected with hsp70 small interfering RNA (siRNA) in order to attenuate Hsp70 expression and activity of NF-κB RelA/p65 was measured using NF-κB consensus bound ELISA. Simultaneous exposures to LPS and celastrol reduced IL-6 expression levels as well as activity of phosphorylated NF-κB at serine 536 (Ser536) in ARPE-19 cells when compared to LPS exposure alone. In addition, inhibition of NF-κB RelA/p65 activity by celastrol was attenuated when Hsp70 response was silenced by siRNA. Favorable 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.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Cell Line
Humans
Pentacyclic Triterpenes
Pigment Epithelium of Eye drug effects
Pigment Epithelium of Eye immunology
Tripterygium chemistry
Anti-Inflammatory Agents immunology
HSP70 Heat-Shock Proteins immunology
Immunity, Innate drug effects
NF-kappa B immunology
Pigment Epithelium of Eye cytology
Triterpenes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-1186
- Volume :
- 64
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Pharmacological research
- Publication Type :
- Academic Journal
- Accession number :
- 21683142
- Full Text :
- https://doi.org/10.1016/j.phrs.2011.05.027