title: HSP60 mediates the neuroprotective effects of curcumin by suppressing microglial activation.
abstract: Curcumin has anti-inflammatory and antioxidant properties and has been widely used to treat or prevent neurodegenerative diseases. However, the mechanisms underlying the neuroprotective effects of curcumin are not well known. In the present study, the effect of curcumin on lipopolysaccharide (LPS)-stimulated BV2 mouse microglia cells was investigated using enzyme-linked immunosorbent assays of the culture medium and western blotting of cell lysates. The results showed that curcumin significantly inhibited the LPS-induced expression and release of heat shock protein 60 (HSP60) in the BV2 cells. The level of heat shock factor (HSF)-1 was upregulated in LPS-activated BV2 microglia, indicating that the increased expression of HSP60 was driven by HSF-1 activation. However, the increased HSF-1 level was downregulated by curcumin. Extracellular HSP60 is a ligand of Toll-like receptor 4 (TLR-4), and the level of the latter was increased in the LPS-activated BV2 microglia and inhibited by curcumin. The activation of TLR-4 is known to be associated with the activation of myeloid differentiation primary response 88 (MyD88) and nuclear factor (NF)-κB, with the subsequent production of proinflammatory and neurotoxic factors. In the present study, curcumin demonstrated marked suppression of the LPS-induced expression of MyD88, NF-κB, caspase-3, inducible nitric oxide synthase, tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in the microglia. These results indicate that curcumin may exert its neuroprotective and anti-inflammatory effects by inhibiting microglial activation through the HSP60/TLR-4/MyD88/NF-κB signaling wpathway. Therefore, curcumin may be useful for the treatment of neurodegenerative diseases that are associated with microglial activation.
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Ningxia 750004, P.R. China.
authors.forename: Feijia
authors.initials: F
authors.lastname: Ding
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Ningxia 750004, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Ningxia 750004, P.R. China.
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, The General Hospital of Ningxia Medical University, Ningxia 750004, P.R. China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Hou
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Ningxia 750004, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Ningxia 750004, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Ningxia 750004, P.R. China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Ma
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Ningxia 750004, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of ICU, The First People's Hospital of Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Lang
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Ningxia 750004, P.R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Ningxia 750004, P.R. China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
keywords: BV2 microglia; Toll-like receptor 4; curcumin; heat shock protein 60