Erythromycin-induced CXCR4 expression on microvascular endothelial cells

Yasuyuki Takagi, Naozumi Hashimoto, Sem H. Phan, Kazuyoshi Imaizumi, Masaki Matsuo, Harunori Nakashima, Izumi Hashimoto, Yuta Hayashi, Tsutomu Kawabe, Kaoru Shimokata, Yoshinori Hasegawa

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Although stromal-derived factor-1 (SDF-1) via its cognate receptor CXCR4 is assumed to play a critical role in migration of endothelial cells during new vessel formation after tissue injury, CXCR4 expression on endothelial cells is strictly regulated. Erythromycin (EM), a 14-membered ring macrolide, has an anti-inflammatory effect that may account for its clinical benefit in the treatment of chronic inflammatory diseases. However, the effects of EM on endothelial cells and especially their expression of CXCR4 have not been fully evaluated. In this study, we demonstrated that EM markedly induced CXCR4 surface expression on microvascular endothelial cells in vitro and lung capillary endothelial cells in vivo. This ability to induce CXCR4 surface expression on endothelial cells was restricted to 14-membered ring macrolides and was not observed in other antibiotics including a 16-membered ring macrolide, josamycin. Furthermore, this EM-induced expression of CXCR4 on endothelial cells was functionally significant as demonstrated by chemotaxis assays in vitro. These findings suggest that EM-induced CXCR4 surface expression on endothelial cells may promote migration of CXCR4-expressing endothelial cells into sites of tissue injury, which may be associated with the known anti-inflammatory activity of this macrolide.

Original languageEnglish
Pages (from-to)L420-L431
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume297
Issue number3
DOIs
Publication statusPublished - 01-09-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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