Angiotensin 1–7, but not the thrombin-cleaved osteopontin C-terminal fragment, attenuates osteopontin-mediated macrophage-induced endothelial-cell inflammation

Rachel Hamias, Assaf Rudich, George Greenberg, Gabriel Szendro, Talya Wolak

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Objective and design: Evaluating the pro-/anti-inflammatory activity of the C-terminal cleavage product of osteopontin in comparison to angiotensin 1–7. Material and subjects: Human coronary endothelial cells (hcEC) treated with conditioned media from human U937 macrophages. Treatment: Macrophages were (pre)treated with C-terminal, full-length or N-terminal osteopontin (OPN-C, OPN-FL, OPN-N, respectively), angiotensin II, angiotensin 1–7 or TNF-α. OPN-C modulatory capacity was compared to that of Ang1–7 in inhibiting subsequent Ag II, OPN-FL or OPN-N-induced macrophage-mediated endothelial inflammation. Methods: Protein expression of NFκB, IκB, vCAM-1 and iCAM-1 was assessed using western blot. Promotor activation by NFκB was also assessed by dual-luciferase reporter assay. Results: Conditioned media of macrophages treated with OPN-C induced hcECs’ NfκB activation to a lower degree than OPN-FL or OPN-N. Priming of macrophages with angiotensin 1–7 attenuated the endothelial pro-inflammatory effect induced by subsequent exposure of the macrophages to angiotensin II, OPN-FL or OPN-N. This was evidenced by both NfκB activation and vCAM and iCAM expression. In contrast, priming macrophages with OPN-C did not significantly attenuate the subsequent response to the pro-inflammatory cytokines. Conclusions: OPN-C induces lower macrophage-induced endothelial inflammation compared to OPN-FL or OPN-N, but unlike angiotensin 1–7, fails to prevent endothelial inflammation induced by subsequent pro-inflammatory macrophage stimulation.

Original languageEnglish
Pages (from-to)265-275
Number of pages11
JournalInflammation Research
Volume67
Issue number3
DOIs
StatePublished - 1 Mar 2018

Keywords

  • IκB
  • NFκB
  • OPN-C terminal
  • OPN-N terminal
  • Osteopontin

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