Sepsis, a systemic inflammatory response syndrome caused by infection, is the most common disease in patients treated in intensive care units. Endotoxic shock, the most critical form of sepsis, is caused by gram-negative bacterial infection. However, the detailed mechanism of endotoxic shock remains unclear. In the present study, we observed that the production of leukotriene B 4 (LTB 4 ) and 12( S )-hydroxyeicosatetraenoic acid (HETE), inflammatory lipid mediators acting on LTB 4 receptors (BLT1 and BLT2), was significantly upregulated in peritoneal lavage fluid (PF) and serum from an LPS-induced endotoxic shock mouse model. Furthermore, BLT1/2-dependent signaling pathways mediated the expression of IL-17, IL-6, and IL-1β, key cytokines for the development of endotoxic shock, via NF-κB activation in the LPS-induced endotoxic shock mouse model. Additionally, inhibition of BLT1/2 significantly attenuated inflammation and tissue damage associated with endotoxic shock and enhanced the survival rate of mice with this inflammatory complication. Together, these results suggest that LTB 4 receptors play critical mediatory roles in the development of endotoxic shock. Our findings point to LTB 4 receptors as potential therapeutic targets for the treatment of endotoxic shock.

No abstract

Mast cells are effector cells in the immune system that play an important role in the allergic airway inflammation. Recently, it was reported that BLT2, a low-affinity leukotriene (LT) B4 receptor, plays a pivotal role in the pathogenesis of allergic airway inflammation through its action in mast cells. We observed that highly elevated expression levels of BLT2 are critical for the pathogenesis leading to allergic airway inflammation, and that if BLT2 expression is downregulated by siBLT2-mediated knockdown, allergic inflammation is dramatically alleviated. Furthermore, we demonstrated that BLT2 mediates the synthesis of vascular endothelial growth factor (VEGF) and Th2 cytokines, such as interleukin (IL)-13, in mast cells during allergic inflammation. Based on the critical roles of BLT2 in mast cells in allergic inflammation, anti-BLT2 strategies could contribute to the development of new therapies for allergic airway inflammation.