| dc.description.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. | en_US |
