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.

<p>Liposomal Encapsulated Curcumin Effectively Attenuates Neuroinflammatory and Reactive Astrogliosis Reactions in Glia Cells and Organotypic Brain Slices</p>

“…71 In vitro, curcumin has previously been shown to reduce the expression of pro-inflammatory mediators and cytokines in activated microglial cells via different signaling pathways. 23,25,[72][73][74][75][76] Curcumin stimulation could also reduce reactivity/activation in astrocytes or astrocytic cell culture models upon different challenges. [77][78][79] In accordance with these findings, we could show that our liposomal curcumin formulation could inhibit LPS-induced cytokine expression by human microglial cells, often even more robust than free curcumin.…”

Curcumin Alleviates Lipopolysaccharide (LPS)-Activated Neuroinflammation via Modulation of miR-199b-5p/IκB Kinase β (IKKβ)/Nuclear Factor Kappa B (NF-κB) Pathway in Microglia

“…Jobin et al showed that curcumin promoted the neuroprotectiove effect afflicted with ischemia by suppressing an inflammatory reaction modulated by the TLR4/p38/MAPK pathway [26]. Also, curcumin resulted in the blockade of lipopolysaccharide (LPS)-activated HSP60/TLR-4/MyD88/NF-κB pathway in BV2 microglia, exerting anti-inflammatory and neuroprotective effects [27]. Similarly, curcumin efficiently attenuated the production of pro-inflammatory mediators nitric oxide (NO) and prostaglandin E-2 (PGE-2), as well as the release of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and TNF-α in LPS-induced microglia [28].…”

Stress Response of Dietary Phytochemicals in a Hormetic Manner for Health and Longevity

“…In mice liver cells with T-cell lymphoma, the expression of GST, GR, and NAD(P)H:quinine oxidoreductase (NQO1) enzymes was increased by activation of curcumin Nrf-2 [44]. Lipopolysaccharide (LPS)-stimulated BV2 mouse microglia cells also inhibited microglial activation by inhibiting the curcumin Hsp60/TLR4/MyD88/NF-κB pathways [45]. As a result, curcumin can show protective effects against cancer, neurodegeneration, and inflammation by acting on stress-response pathways.…”