Intervention with VG1177, a MHC Class II Invariant Peptide Chain (CLIP) Antagonist, Restores Afferent Arteriolar Autoregulatory Behavior during Chronic 14 Day Lipopolysaccharide Treatment

Lipopolysaccharide (LPS) is a cell wall component of gram-negative bacteria that is a known ligand for toll-like receptor 4, which, in turn, activates the innate immune system. MHC Class II-associated invariant peptide (CLIP) is critically linked to antigen processing, presentation, and adaptive immune system activation. Chronic immune system activation and inflammation are linked to blunted afferent arteriolar autoregulatory behavior and kidney injury. Previous work established that afferent arteriolar autoregulatory behavior is impaired following 7 days of LPS treatment by osmotic minipump, while simultaneous co-treatment with VG1177 preserved autoregulatory capability. Accordingly, we postulated that competitive CLIP antagonist (VG177) treatment could rescue autoregulatory behavior impaired by chronic low-dose LPS exposure. Osmotic minipumps were implanted (day 0) for infusion of LPS (0.01mg/kg/day) or saline (0.9% NaCl) for 14 days and then kidneys were harvested for juxtamedullary nephron studies. Th...