The family of interleukin 17 receptors (IL17Rs), subtypes IL17RA-IL17RE, is 
targeted by the group of pro-inflammatory IL17 cytokines (IL17A-F) and moreover 
the newly developed anti-IL17A antibody secukinumab (AIN457) has shown promise 
in Phase II trials in multiple sclerosis. Here, we show that human astrocytes, 
isolated from a fetal cerebral cortex, express IL17RA and IL17RC and in vitro 
treatment with IL17A increases protein levels of IL6 in human astrocytes, which 
is enhanced in the presence of TNFα, as determined by homogeneous time resolved 
fluorescence. Studies on acutely isolated mouse astrocytes are comparable to 
human astrocytes although the protein levels of IL6 are lower in mouse 
astrocytes, which also show a lower response to IL17F and IL1β in promoting IL6 
levels. In human astrocytes, IL17A and TNFα also induce mRNA expression of IL6, 
IL8 and the Th17 cytokines CXCL1, CXCL2, and CCL20, with little effect on Th1 
cytokines CXCL9, CXCL10, and CXCL11. The effects of IL17A are associated with 
nuclear translocation of the NF-κB transcription factor, as determined by 
immunocytochemistry, where treatment of human astrocytes with the inhibitors of 
the NF-κB pathway and with secukinumab inhibits the IL17A and IL17A/TNFα-induced 
increase in nuclear translocation of NF-κB and levels of IL6. Taken together the 
data shows that IL17A signaling plays a key role in regulating the levels of 
cytokines, such as IL6, in human astrocytes via a mechanism that involves NF-κB 
signaling and that selective inhibition of IL17A signaling attenuates levels of 
pro-inflammatory molecules in astrocytes.