n-butanol extract from Folium isatidis inhibits the lipopolysaccharide-induced downregulation of CXCR1 and CXCR2 on human neutrophils

Wu, Beibei; Wang, Liyin; Jiang, Lili; Dong, Lili; Xu, Fengli; Lu, Yili; Jin, Jiahui; Wang, Zhanyue; Liang, Guang; Shan, Xiaoou

Polymorphonuclear neutrophils (PMNs) are an essential component of the innate immune system, involved in the clearance of extracellular pathogens (5) . As the most abundant subset of leukocytes, the involvement of PMN in sepsis is significant (3, 6, 7) . The migration of PMNs is regulated by chemoattractants and chemokine gradients (3, 7, 8) . CXC-chemokine receptor (CXCR)1 and CXCR2 are the major chemokine receptors on PMNs, with interleukin (IL)-8 acting as a ligand of these receptors (9) . Severe sepsis is associated with the failure of PMNs to migrate (10) . In a previous clinical study, patients with suppression of PMN receptors were predisposed to inflammatory response syndrome (11) . Previous in vitro investigations have demonstrated that CXCR2 is downregulated upon stimulation with tumor necrosis factor-α (TNF-α) (12) . The activation of Toll-like receptor 4 (TLR4) also suppresses the expression of CXCR2 (13) . In an experimental mouse model of sepsis, the failure of PMNs to migrate was shown to result in a high rate of mortality (1). Tancevski et al and Van Zee et al reported that promoting the recruitment of PMNs ameliorates sepsis and attenuates sepsis-related injury and infection, respectively (14, 15) . Therefore, in order to improve treatment of inflammatory disorders, including sepsis, the promotion of PMN chemotaxis is an attractive target (6).