Background: IL-22 promotes wound healing in the gut and skin but there is a lack of knowledge in lung. This study therefore investigated the impacts of IL-22 on lung epithelial cell proliferation, in vitro, and investigated the underlying cellular signalling cascades. The bleomycin-induced lung fibrosis model was used to assess changes in endogenous IL-22 during wound repair in lung.
Methods: To investigate cell proliferation, A549 human lung carcinoma cells were treated with IL-22 at 25, 50, and 100 ng/ml concentrations for 118 h and growth was observed using live-cell imaging. Signal transduction through activation of STAT1/3/5, Akt, and MAPKs were also determined 15 and 30 min after treatment (50 ng/ml). The downstream effectors including cellular stress markers like GRP78, sXBP1, and NOS2 were then assessed after 6, 12, and 24 h of exposure. 5-6 week old C57BL/6 mice were administered 0.15 U of bleomycin sulfate via the intranasal route. Body weight was monitored daily and animals were sacrificed at 3, 7, 14, and 21 days following bleomycin-administration. At each time point, lung weight and gross morphology were recorded. The same lung lobes were analyzed histologically and using q-RT-PCR to monitor Il22 gene expression.
Results and Conclusions: IL-22 significantly (p<0.05 at 50 and p<0.001 at 25 ng/ml) induced proliferation of A549 cells. IL-22 also activated multiple signalling pathways including STAT1, STAT3 (p<0.001) and p38 MAPK (p<0.05) within 15 min of treatment. However, IL-22 treatment did not significantly change expression of cellular stress markers. Intranasal administration of bleomycin caused sustained body weight loss, and lung pathology, including oedema and thickening of bronchiolar walls. Il22 mRNA level increased at day 3 (p<0.01) and then decreased with time, remaining elevated 7 days post-injury. These results indicate that IL-22 may play an important role in switching on epithelial wound repair in the damaged lung.