Interaction of IL-22/IL-22R1 promotes cell proliferation and suppresses apoptosis of colorectal cancer via phosphorylation of STAT3

Interleukin-22 (IL-22) is a member of IL-10 cytokine family which is expressed in activated T cellspredominantly and in activated natural killer cells at lower levels. Previous studies have demonstrated the link betweenelevated levels of IL-22 and disease severity of psoriasis, Crohn’s disease, rheumatoid arthritis and interstitial lungdiseases. However, the function of IL-22 in the development and progression of colorectal cancer (CRC) remainselusive. In this study, we first evaluated the IL-22/IL-22R1 level in CRC patients, and found that tumor tissueshave more active expression of IL-22 and IL-22R1 than normal tissues, presenting correlation with the degree ofdifferentiation of tumor tissues. Subsequently, Caspase and cell viability assays were performed on SW-480 cell linewhich expresses high level of IL-22R1 to examine if the supplementation of IL-22 has an impact on apoptosis andproliferation. In comparison with treatment of 5-FU, supplementation of IL-22 promoted cell proliferation andameliorated apoptosis. To unveil signal transduction upon activation of IL-22R, we examined the phosphorylationof STAT3 in SW-480 cell line following supplementation of IL-22. The treatment of IL-22 also increased the level ofp-Akt, an essential component in PI3K/Akt pathway. Although the link between STAT3 phosphorylation and PI3K/Akt activation remains to be explored, our study revealed the mechanism underlying the effects of IL-22R activation onapoptosis as well as tumor differentiation, indicating the prognostic value of IL-22/IL-22R.