ABSTRACT
AIM:To investigate the biological function and potential mechanism of leucine-rich repeat kinase 2 (LRRK2)in RAW264.7 macrophages during Mycobacterium tuberculosis infection.METHODS: The bacillus Calmette-Guerin(BCG)-infected RAW264.7 cell model was established.Colony-forming unit(CFU)analysis was used to deter-mine the mycobacterial viability.The releases of interleukin(IL)-1β,IL-6 and interferon-γ(IFN-γ)in the RAW264.7 cells were detected by ELISA.qPCR and Western blot were used to measure the mRNA and protein expression levels,re-spectively.RESULTS:LRRK2 was robustly enhanced in the RAW264.7 cells in response to BCG infection.Additional-ly,silencing of LRRK2 suppressed intracellular growth of mycobacteria during BCG challenge.Moreover, silencing of LRRK2 dramatically attenuated the accumulation of inflammatory cytokines IL-1β,IL-6 and IFN-γinduced by BCG infec-tion.More importantly,LRRK2 modulated BCG-induced inflammatory responses by positively regulating the nuclear factor-κB(NF-κB)signaling pathway.CONCLUSION: LRRK2/NF-κB signaling pathway positively modulates inflammatory responses during BCG infection,which may provide a better understanding of the pathogenesis of tuberculosis and useful in -formation for developing potential therapeutic interventions against the disease.