Interleukin-22: a potential immunomodulatory molecule in the lung.
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.
Whittington
Hayley A
HA
Lung Research Group, Department of Clinical Sciences North Bristol, University of Bristol, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK.
Armstrong
Lynne
L
Uppington
Kay M
KM
Millar
Ann B
AB
D001483:Base Sequence; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000502:physiology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D000097043:Interleukin-22
D004268:DNA-Binding Proteins; D007378:Interleukins; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D000097043:Interleukin-22; C494086:STAT3 protein, human