VEGFR1 Signaling Regulates IL-4-Mediated Arginase 1 Expression in Macrophages.

Background: Macrophages undergo polarization or activation in response to environmental stimuli, an essential process for proper immune response. Meanwhile, excessive activation of macrophages causes autoimmune diseases. It is therefore crucial to prevent over-activation of macrophage in order to maintain the proper immune response. Arginase 1 (Arg-1) plays a critical role in coordinating the immune response by regulating availability of arginine. Objective: To understand the mechanism of Arg-1 regulation. Methods: Real-time PCR and Western Blot analysis were utilized to examine the Arg-1 levels expressed from the VEGFR1-deleted and VEGFR1-TK-deficient bone marrow-derived macrophages (BMDMs). Results: The VEGFR1-mediated signaling suppressed IL-4-induced Arg-1 expression. Deletion of VEGFR1 resulted in elevated Arg-1 expression and the tyrosine kinase domain of VEGFR1 was required for the suppression. Each of three ligands of VEGFR1, VEGF-A, VEGF-B and PIGF, mediated the inhibition to the similar degree. Conclusion: Our findings identified a novel function of the VEGFR1 signaling in avoiding over-expression of Arginase 1 potentially to maintain the proper innate immune response.