Inhibiting expression of HSP60 and TLR4 attenuates paraquat-induced microglial inflammation

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Microglia play a crucial role in neuroinflammation.
• Heat shock protein 60 (HSP60) and toll-like receptor 4 (TLR4) are implicated in inflammatory responses.
• Paraquat (PQ) exposure can induce microglial inflammation via the HSP60-TLR4-Myd88-NF-κB pathway.

Purpose of the Study:

• To investigate the modulatory roles of HSP60 and TLR4 in paraquat-induced microglial inflammation.
• To determine if inhibiting HSP60 or TLR4 can attenuate PQ-evoked inflammatory responses.

Main Methods:

• Microglia BV2 cells were pretreated with siRNA to knockdown HSP60 or with a TLR4 inhibitor before PQ exposure.
• Expression of TLR4, MyD88, and nuclear translocation of NF-κB p65 were analyzed using immunoblotting and immunofluorescence.
• Quantitative real-time PCR was used to assess the expression of pro-inflammatory factors (TNF-α, IL-1β, IL-6, iNOS).

Main Results:

• Knockdown of HSP60 or inhibition of TLR4 significantly reduced TLR4 and MyD88 expression.
• Inhibition of HSP60 or TLR4 decreased the nuclear accumulation of NF-κB p65.
• PQ-induced gene expression of TNF-α, IL-1β, IL-6, and iNOS was significantly attenuated by HSP60 knockdown or TLR4 inhibition.

Conclusions:

• HSP60 and TLR4 are key modulators of intracellular signaling in paraquat-induced microglial inflammation.
• Targeting HSP60 or TLR4 represents a potential therapeutic strategy to reduce inflammation in PQ-activated microglia.