Interleukin-22: a potential immunomodulatory molecule in the lung

Am J Respir Cell Mol Biol. 2004 Aug;31(2):220-6. doi: 10.1165/rcmb.2003-0285OC. Epub 2004 Mar 23.

Abstract

Interleukin (IL)-22 is a member of the human type I interferon family, which includes IL-10. IL-22 has the potential to interact with IL-10 because it binds to the IL-10R2c chain with IL-22R1 in its receptor complex. Binding can be blocked by the soluble receptor, IL-22 binding protein (IL-22BP). We hypothesize that IL-22 and IL-22BP are involved in inflammatory regulation and its subsequent role in the pathogenesis of inflammatory lung disease. We have demonstrated IL-22 mRNA expression in alveolar macrophages (AM), monocytes, and alveolar epithelial (AE) cells. IL-22BP mRNA is expressed in AM, AE cells, and neutrophils. In contrast, IL-22R1 is expressed in AE only. Immunohistochemistry on normal and interstitial lung disease lung sections has confirmed IL-22 protein expression. Western blotting for IL-22 in bronchoalveolar lavage fluid demonstrated that lower levels of IL-22 were present in patients with acute respiratory distress syndrome and sarcoidosis relative to control subjects (P = 0.0152 and P = 0.0213). Levels of IL-22 in idiopathic pulmonary fibrosis were not different than those of the control subjects (P = 0.5838). IL-22 did not affect IL-10 inhibition of tumor necrosis factor-alpha in monocytes, which do not express IL-22R1. By contrast, we demonstrated synergy between IL-10 and IL-22 in terms of IL-8 inhibition in IL-22R1-expressing A549 cells. These data suggest a role for IL-22 in the regulation of pulmonary inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blotting, Western
  • DNA-Binding Proteins / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunohistochemistry
  • Interleukins / physiology*
  • Molecular Sequence Data
  • Phosphorylation
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor
  • Trans-Activators / metabolism

Substances

  • DNA-Binding Proteins
  • Interleukins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • interleukin-22