NLRC4 gene silencing-dependent blockade of NOD-like receptor pathway inhibits inflammation, reduces proliferation and increases apoptosis of dendritic cells in mice with septic shock.

Septic shock is one of the most significant health concerns across the world, involving hypo-perfusion and defects in tissue energy. The current study investigates the role of NLR family CARD domain containing protein 4 (NLRC4) in septic shock-induced inflammatory reactions, lung tissue injuries, and dendritic cell (DC) apoptosis. Septic shock mice models were established by modified cecal ligation and puncture and injected with retroviral vector expressing siRNA-NLRC4. DCs were then isolated and transfected with siRNA-NLRC4. The degree of lung tissue injury, cell cycle distribution, cell apoptosis and cell viability of DCs were assessed. NLRC4 was found to be expressed at high levels in mice with septic shock. NLRC4 silencing inhibited the activation of the NOD-like receptor (NLR) pathway as evidenced by the decreased levels of NOD1, NOD2, RIP2, and NF-κB. In addition, NLRC4 silencing reduced the inflammatory reaction as attributed by reduced levels of IL-1β, TNF-α and IL-6. Suppressed NLRC4 levels inhibited cell viability and promoted cell apoptosis evidenced by inhibited induction of DC surface markers (CD80, CD86, and MHC II), along with alleviated lung tissue injury. In conclusion, NLRC4 silencing ameliorates lung injury and inflammation induced by septic shock by negatively regulating the NLR pathway.