The role of Interleukin-22 and its receptor Interleukin-22Rα on the regulation of inflammatory responses in the brain

Abstract Interleukin (IL)-22 is a member of IL-10 family, is a potent mediator of inflammatory responses. It is produced by activated CD4+ T cells and natural killer (NK) cells and takes effect on non-hematopoietic cells mainly stromal and epithelial cells. And, IL-22 receptor consists of IL-22Rα and IL-10Rβ. It is known that IL-22Rα expression is restricted to non-hematopoietic cells in the skin, pancreas, intestine, liver, lung and kidney. Even though IL-22 is mainly involved in the development of inflammatory responses, but there is a no report regarding their roles on inflammatory responses in the brain. In the present study, I investigated the role of IL-22 and its receptor on inflammatory responses in the brain using mouse microglia cell line, BV2 and mouse hippocampal neuronal cell line, HT22. When BV2 and HT22 were treated with rIL-22 (20 ng/ml), expression of cyclooxygenase (COX)-2, was increased and its expression is followed by the increased of PGE2 production. Next, I examined whether production of pro-inflammatory cytokines, such as such as IL-6 and TNF-α, and pro-inflammatory chemokines by IL-22 treatment. As a result, I confirmed that IL-6, TNF-α, and MIG/CXCL9 are remarkably increased. Taken together, IL-22α is spontaneously expressed on the cells, especially microglia and neuron and it is closely involved in the development of inflammatory responses in the brain.