C5b-9 membrane attack complex activated NLRP3 inflammasome mediates renal tubular immune injury in trichloroethylene sensitized mice

Abstract

Trichloroethylene (TCE) induced occupational medicamentosa-like dermatitis (OMLDT) in patients is accompanied, typically, by renal damage. But the role of C5b-9 and IL-1β in TCE-sensitized mouse renal tubular damage is unclear. This study aimed to investigate whether TCE-sensitized mouse renal tubular epithelial cell damage was induced by NLRP3 inflammasome and whether NLRP3 inflammasome was activated by sublytic C5b-9. In total, 52 specific pathogen-free BALB/c female mice, 6- to 8-week-old, were used for establishing the TCE-sensitized mouse model. Renal tubular epithelial cells were isolated and used for determining the sublytic level of C5b-9. Kidney histological examination, serum neutrophil gelatinase associated lipocalin (NGAL) level were used for kidney damage evaluation. Renal protein levels of C5b-9, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 were measured. The renal lesions, serum NGAL level, renal NLRP3, ASC, Caspase-1 and IL-1β protein levels all increased significantly in TCE sensitized positive group. However, pretreatment with recombinant protein sCD59-Cys inhibited the expression of C5b-9, NLRP3 inflammasome, IL-1β, IL-18, and attenuated renal tubular epithelial cell damage. The sublytic C5b-9 activated NLRP3 inflammasome and aggravated renal tubular epithelial cell damage. Pretreatment with recombinant protein sCD59-Cys blocked the expression of the NLRP3 inflammasome by inhibiting the expression of C5b-9, and alleviating renal tubular epithelial cell damage.

Keywords: C5b-9 membrane attack complex; CD59; Immune injury; NLRP3 inflammasome; Renal tubular epithelial cells; Trichloroethylene.