Interleukin-17A-mediated alleviation of cortical astrocyte ischemic injuries affected the neurological outcome of mice with ischemic stroke.

We previously reported that astrocytes are the main sources of interleukin (IL)-17A production that could aggravate neuronal injuries in ischemic stroke. However, the effects of IL-17A on ischemic astrocytes themselves and the underlying molecular mechanism are still unclear. In this study, we found that recombinant mouse (rm) IL-17A could significantly (P<0.05 or <0.001) alleviate 1-hour oxygen-glucose deprivation (OGD)/reoxygenation (R) 24-hour-induced ischemic injuries in cortical astrocytes with a dose-dependent manner (n=6 per group). The Western blot and cell cycle analysis results revealed that rmIL-17A significantly (P<0.05) inhibited procaspase-3 cleavage without affecting cell proliferation in 1-hour OGD/R 24-hour-treated cortical astrocytes (n=6 per group). Among the five IL-17 receptor subunits (IL-RA, -RB, -RC, -RD, and -RE), only IL-17RA (P<0.01) and -17RC (P<0.05) membrane translocation (not messenger RNA and protein) levels were downregulated in cortical astrocytes following 1-hour OGD/reperfusion 24hours, and rmIL-17A could significantly (P<0.05 or <0.001) inhibit this downregulation (n=6 per group). To further verify the impact of IL-17A on the neurological outcome of ischemic stroke, we found that the intracerebroventricular injection of IL-17A neutralizing monoclonal antibody remarkably (P<0.001) reduced the astrocyte activation and improve neurological function (P<0.05 or <0.01) of mice following 1-hour middle cerebral artery occlusion/reperfusion (R) 3 to 7 days (n=6 or 8 per group). These results suggested that IL-17A-mediated alleviation of cortical astrocyte ischemic injuries could affect the neurological outcome of mice with ischemic stroke, which might be mainly dependent on the cell apoptosis pathway through inhibiting the downregulation of IL-17RA and -17RC membrane translocations.