Innate and acquired immune responses are both necessary to clear bacterial pathogens and to generate the inflammatory cascade that contributes to osteoclastogenic bone loss—a hallmark of periodontal disease. p38 mitogen-activated protein kinases (MAPKs) are critical for innate immune signaling and subsequent cytokine expression in periodontal inflammation and bone destruction. Li et al. evaluated the therapeutic potential of targeting a downstream substrate of p38, MK2 (mitogen-activated protein kinase-activated protein kinase 2), using intraoral RNA interference by administration of small interfering RNA (siRNA) against MK2. Intraoral administration of MK2 siRNA demonstrated that silencing MK2 modulates the innate immune response triggered by bacterial lipopolysaccharide, intraoral delivery of covalently-modified siRNA is effective for inhibiting target gene expression in vivo, and siRNA-mediated inhibition of MK2 decreases periodontal disease severity in vivo. This is the first study to demonstrate that MK2 is critical in the pathogenesis of periodontitis and to evaluate the therapeutic potential of modulating MK2 activity in a periodontal disease model using a covalently modified siRNA. This proof-of-concept study suggests a novel target, MK2, using an intraoral RNA interference strategy to control periodontal inflammation.
See article at J Pharmacol Exp Ther 2011, 336:633–642.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics