Interleukin-4 Induces Lipogenesis in Porcine Endothelial Cells, Which in Turn is Critical for Induction of Protection Against Complement-Mediated Injury

S. M. Black, M. E. Schott, B. A. Benson, M. S. Rutherford, B. K. Levay Young, A. P. Dalmasso

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Interleukin (IL)-4 has been shown to induce protection in porcine vascular endothelial cells (ECs) from killing by human complement. This protection is dependent on the PI3K/Akt signaling pathway. In this study, we investigated mechanisms downstream of Akt and found that activation of the lipid biosynthesis pathway is required for protection from complement in ECs treated with IL-4. Cells incubated with IL-4 for 48 hours contained increased fatty acids and phospholipids but cholesterol was not increased when compared with medium-treated controls. The transcription factor SREBP-1, which regulates fatty acid synthesis, was found to be activated in extracts of ECs incubated with IL-4 for 6 hours. Finally, induction of protection from complement killing with IL-4 was fully prevented by the presence of the SREBP inhibitor 25-OH cholesterol. This study showed that IL-4 induces lipid biosynthesis in porcine ECs through activation of SREBP-1 and that the activation of this pathway is critical for IL-4 to induce protection of porcine ECs from killing by human complement. Further study of these mechanisms may provide new strategies for the prevention of complement-mediated vascular injury as it occurs in xenograft rejection.

Original languageEnglish (US)
Pages (from-to)638-640
Number of pages3
JournalTransplantation proceedings
Volume40
Issue number2
DOIs
StatePublished - Mar 2008

Bibliographical note

Funding Information:
Supported by grants from NIH and Minnesota Medical Foundation. SMB was supported by a NRSA from NIH.

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