Gas6/AXL Modulates Increased Inflammatory Cytokines During Preeclampsia in Rats

Preeclampsia (PE) is a complicated obstetric complication characterized by increased blood pressure and the production of inflammatory cytokines. The growth arrest‐specific 6 (Gas6) protein is known to induce dynamic cellular responses and is elevated in PE. Gas6 binds to the AXL tyrosine kinase receptor and AXL‐mediated signaling is implicated in proliferation and migratory mechanisms in several tissues. Our laboratory utilized Gas6 to induce preeclamptic conditions in pregnant rats. Our objective was to determine the role of Gas6 and AXL signaling in the release of cytokines during the development of PE in the rat. Briefly, pregnant rats were divided into 3 groups that received daily ip injections of PBS, Gas6, or Gas6 + R428 (an AXL inhibitor). Treatment was done from embryonic day 7.5 (E7.5) to E18.5, at which time they were euthanized and serum was harvested for Multiplex cytokine determination. Fetal and placental weights were recorded. Blood pressure and proteinuria were determined. We observed: increased proteinuria and elevated blood pressure in Gas6 treated animals, but each were inhibited by R428; a 12‐fold increase of serum interferon gamma was reduced by AXL inhibition; a 12‐fold increase in serum IL1‐alpha was inhibited by AXL inhibition; a 45‐fold increase in serum IL‐2 was reduced by AXL inhibition; a 10‐fold increase in serum IL1‐beta was reduced by AXL inhibition; a 29‐fold increase in serum IL4 was decreased by AXL inhibition; a 13‐fold increase in serum IL5 was reduced by AXL inhibition; an 24‐fold increase in serum IL6 was reduced by AXL inhibition; and a 20‐fold increase in IL12p70 was reduced by AXL inhibition. These data suggest roles for Gas6/AXL in cytokine elaboration coincident with PE and offer possible treatment avenues that may alleviate PE symptoms. Support or Funding Information This work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI, PRR and JAA) and a BYU Mentoring Environment Grant (JAA and PRR). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .