Effect of lipoxin A4 methyl ester from arachidonic acid on JAK2/STAT3 pathway after cerebral ischemia-reperfusion injury

Abstract

It was determined if lipoxin A4 methyl ester (LXA4 ME) affects JAK2/STAT3 pathway following transient focal cerebral ischemia-reperfusion injury (CIRI) in rats. Adult male SD rats were randomly assigned to sham-operated, CIRI group, DMSO + CIRI, AG490 + CIRI, and LXA4 ME + CIRI. Neurologic deficit was evaluated in rats after 24 h reperfusion. IL-6 levels of brain tissue were determined 6 and 24 h post-reperfusion using an ELISA assay. STAT3 and SOCS3 mRNA levels were analyzed via real-time quantitative PCR. P-JAK2, p-STAT3, and SOCS3 were measured via Western blotting, and localized by fluorescent immunohitochemistry. Transient cerebral ischemia in rats caused a significantly elevated concentration of IL-6, levels of STAT3 and SOCS3 mRNA, phosphorylation of JAK2 and STAT3, and immunoreactive glia of ipsilateral cortex 24 h post-reperfusion versus sham rats. The AG490 intervention downregulated cerebral ischemia-induced JAK2 and STAT3 phosphorylation, and their immunoreactive glia located in the ischemic cortex. LXA4 ME reduced the concentration of IL-6, increased SOCS3 expression, inhibited phosphorylation and immunoreactive glia of JAK2 and STAT3, as well as ameliorated neurologic dysfunction. In conclusions, LXA4 ME inhibited JAK2/STAT3 activation, perhaps via upregulating SOCS3, as well as suppressed IL-6 expression to ameliorate cerebral ischemic injury.