S100-alarmins: potential therapeutic targets for arthritis

Expert Opin Ther Targets. 2017 Jul;21(7):739-751. doi: 10.1080/14728222.2017.1330411. Epub 2017 May 25.

Abstract

In arthritis, inflammatory processes are triggered by numerous factors that are released from joint tissues, promoting joint destruction and pathological progression. During inflammation, a novel family of pro-inflammatory molecules called alarmins is released, amplifying inflammation and joint damage. Areas covered: With regard to the role of the alarmins S100A8 and S100A9 in the pathogenesis of arthritis, recent advances and the future prospects in terms of therapeutic implications are considered. Expert opinion: There is still an urgent need for novel treatment strategies addressing the local mechanisms of joint inflammation and tissue destruction, offering promising therapeutic alternatives. S100A8 and S100A9, which are the most up-regulated alarmins during arthritis, are endogenous triggers of inflammation, defining these proteins as promising targets for local suppression of arthritis. In murine models, the blockade of S100A8/S100A9 ameliorates inflammatory processes, including arthritis, and there are several lines of evidence that S100-alarmins may already be targeted in therapeutic approaches in man.

Keywords: Alarmins; S100A8; S100A9; new diagnostic tools; rheumatoid arthritis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis / drug therapy*
  • Arthritis / physiopathology
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / physiopathology
  • Calgranulin A / metabolism*
  • Calgranulin B / metabolism*
  • Disease Progression
  • Drug Design
  • Humans
  • Inflammation / drug therapy
  • Inflammation / physiopathology
  • Mice
  • Molecular Targeted Therapy
  • Up-Regulation

Substances

  • Calgranulin A
  • Calgranulin B