Abstract
Ischemia-reperfusion frequently occurs in ischemic cerebral vascular disease, during which the inflammatory signaling plays essential roles. The aim of this study was to discover the efficacy of the antibody to a key immune cytokine IL-23 (anti-IL-23) for the therapy of cerebral ischemia-reperfusion injury. We established the cerebral ischemia-reperfusion injury model by middle cerebral artery occlusion (MCAO). Anti-IL-23 injection attenuated lesions indicated by histology study. RT-PCR and Western blot were employed to detect the mRNA and protein expression of JAK2 and STAT3 after anti-IL-23 treatment. ELISA was utilized to measure the levels of MDA (malondialdehyde) and superoxide dismutase (SOD). Moreover, curcumin and IL-6 were implicated in the endogenous intervention of IL-23 signaling in vivo. Our data demonstrated that the treatment of anti-IL-23 might transcriptionally activate the classic immune pathway in the brain. Anti-IL-23 augmented phosphorylation levels of both JAK2 and STAT3, suggesting the amplification signaling of JAK/STAT after exogenous IL-23 intervention. Anti-IL-23 reduced ROS molecules of STAT downstream in the serum and brain. It also alleviated the injury by bringing down levels of MDA and SOD in the serum. JAK2 inhibitor could abolish the effect of anti-IL-23 whereas JAK3 ameliorated the injury. The combination of anti-IL-23 and JAK3i could reduce infarct volume more effectively. In summary, this study indicated that anti-IL-23 had protective effects against cerebral ischemia-reperfusion injury by targeting the immune specific JAK2-STAT3 in JAK/STAT pathway.
Highlights
Ischemia-reperfusion is frequently occurred in ischemic cerebral vascular disease, during which process the inflammatory signaling played essential roles
Anti-IL-23 augment the phosphorylation levels of both JAK2 and STAT3, suggesting the amplification signaling of JAK/STAT after exogenous IL-23 intervention
This study indicated that anti-IL-23 had protection effects against cerebral ischemiareperfusion injury by targeting the immune specific JAK2-STAT3 in JAK/STAT pathway
Summary
Ischemia-reperfusion is frequently occurred in ischemic cerebral vascular disease, during which process the inflammatory signaling played essential roles. The aim of study was to discover the efficacy of the antibody to a key immune cytokine IL-23 (anti-IL-23) for the therapy of cerebral ischemia-reperfusion injury. Cerebral vascular diseases, such as cerebral hemorrhage and cerebral ischemia are severe neural diseases which could result in disability and mortality [1, 2]. Multiple molecular mechanisms are involved in the ischemia induced injury caused by insufficient blood supply in brain vessels, including neural apoptosis, DNA damage, neurotransmitter release, oxidative stress and hypoxia 4. Neuroprotective agents derived from natural herbs with anti-inflammatory and anti-oxidant activities could alleviate neural damage nerve injury after cerebral ischemia-reperfusion injury through inhibiting apoptosis and inflammation [11, 12]. Besides the chemical inhibitors or natural compound, agents such as pure proteins or targeted antibodies might contribute to the protection against cerebral ischemiareperfusion injury [13, 14]
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