Please use this identifier to cite or link to this item:
http://repository.unisma.ac.id/handle/123456789/2034
Title: | Exogenous Heat Shock Cognate Protein 70 Suppresses LPS-Induced Inflammation by Down-Regulating NF-κB through MAPK and MMP-2/-9 Pathways in Macrophages |
Authors: | Sulistyowati, Erna Lee, Mei-Yueh Wu, Lin-Chi Hsu, Jong-Hau Dai, Zen-Kong Wu, Bin-Nan Lin, Ming-Chung Yeh, Jwu-Lai |
Keywords: | Heat Shock Protein Llipopolysaccharide Inflammation RAW264.7 Macrophages Matrix Metalloproteinases |
Issue Date: | 23-Aug-2018 |
Publisher: | MDPI journals |
Series/Report no.: | MDPI journals;Vol.23, Issue 9, Page 1-13 |
Abstract: | Heat shock cognate protein 70 (HSC70), a molecular chaperone, is constitutively expressed by mammalian cells to regulate various cellular functions. It is associated with many diseases and is a potential therapeutic target. Although HSC70 also possesses an anti-inflammatory action, the mechanism of this action remains unclear. This current study aimed to assess the anti-inflammatory effects of HSC70 in murine macrophages RAW 264.7 exposed to lipopolysaccharides (LPS) and to explain its pathways. Mouse macrophages (RAW 264.7) in 0.1 µg/mL LPS incubation were pretreated with recombinant HSC70 (rHSC70) and different assays (Griess assay, enzyme-linked immune assay/ELISA, electrophoretic mobility shift assay/EMSA, gelatin zymography, and Western blotting) were performed to determine whether rHSC70 blocks pro-inflammatory mediators. The findings showed that rHSC70 attenuated the nitric oxide (NO) generation, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) expressions in LPS-stimulated RAW264.7 cells. In addition, rHSC70 preconditioning suppressed the activities and expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9. Finally, rHSC70 diminished the nuclear translocation of nuclear factor-κB (NF-κB) and reduced the phosphorylation of extracellular-signal regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPK), and phosphatidylinositol-3-kinase (PI3K/Akt). We demonstrate that rHSC70 preconditioning exerts its anti-inflammatory effects through NO production constriction; TNF-α, and IL-6 suppression following down-regulation of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and MMP-2/MMP-9. Accordingly, it ameliorated the signal transduction of MAPKs, Akt/IκBα, and NF-κB pathways. Therefore, extracellular HSC70 plays a critical role in the innate immunity modulation and mechanisms of endogenous protective stimulation. |
Description: | [ARCHIVES] Copyright Article from: MDPI journals |
URI: | https://www.mdpi.com/1420-3049/23/9/2124 http://repository.unisma.ac.id/handle/123456789/2034 |
Appears in Collections: | LP - Medical Education |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
dr. Erna-4- molecules-23-02124.pdf | Document | 2.22 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.