An innate interaction between IL-18 and the propeptide that inactivates its precursor form

Sci Rep. 2019 Apr 16;9(1):6160. doi: 10.1038/s41598-019-42661-5.

Abstract

Uncontrolled secretion of mature interleukin (IL)-1β and IL-18 is responsible for severe autoinflammatory or autoimmune disorders and various allergic diseases. Here we report an intramolecular interaction between IL-18 and its propeptide, which is proteolytically removed from its precursor proIL-18 during maturation. The intramolecular interaction was recapitulated intermolecularly using recombinant propeptide. These results suggest the possibility of developing a novel class of peptide-based IL-18 inhibitors that could serve as therapeutic agents for IL-18-related inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Humans
  • Interleukin-18 / chemistry
  • Interleukin-18 / metabolism*
  • Models, Molecular
  • Peptides / chemistry
  • Peptides / metabolism
  • Protein Precursors / chemistry
  • Protein Precursors / metabolism*
  • Protein Stability
  • Proteolysis

Substances

  • IL18 protein, human
  • Interleukin-18
  • Peptides
  • Protein Precursors