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Doxycycline Inhibits Polarization of Macrophages to the Proangiogenic M2-type and Subsequent Neovascularization

He, Lizhi ; Marneros, Alexander G.

The Journal of biological chemistry, 2014-03, Vol.289 (12), p.8019-8028 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Doxycycline Inhibits Polarization of Macrophages to the Proangiogenic M2-type and Subsequent Neovascularization
Autor: He, Lizhi ; Marneros, Alexander G.
Assuntos: Angiogenesis ; Angiogenesis Inhibitors - pharmacology ; Angiogenesis Inhibitors - therapeutic use ; Animals ; Anti-Bacterial Agents - pharmacology ; Anti-Bacterial Agents - therapeutic use ; Antibiotics ; Cell Line ; Cell Survival - drug effects ; Cells, Cultured ; Choroidal Neovascularization - drug therapy ; Choroidal Neovascularization - pathology ; Dinoprostone - immunology ; Doxycycline - pharmacology ; Doxycycline - therapeutic use ; Female ; Humans ; Immunology ; Inflammation ; Innate Immunity ; Interleukin-13 - immunology ; Interleukin-1beta - immunology ; Interleukin-4 - immunology ; Macrophages ; Macrophages - drug effects ; Macrophages - immunology ; Macrophages - pathology ; Macular Degeneration ; Male ; Mice ; Mice, Inbred C57BL ; Wound Healing
É parte de: The Journal of biological chemistry, 2014-03, Vol.289 (12), p.8019-8028
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Macrophages occur along a continuum of functional states between M1-type polarized macrophages with antiangiogenic and antitumor activity and M2-type polarized macrophages, which have been implicated to promote angiogenesis and tumor growth. Proangiogenic M2-type macrophages promote various pathologic conditions, including choroidal neovascularization in models of neovascular age-related macular degeneration, or certain cancers, such as glioblastoma multiforme. Thus, a potential novel therapeutic approach to target pathological angiogenesis in these conditions would be to inhibit the polarization of macrophages toward the proangiogenic M2-type. However, no pharmacological inhibitors of M2-type macrophage polarization have been identified yet. Here we performed an unbiased pharmacological and small chemical screen to identify drugs that inhibit proangiogenic M2-type macrophage polarization and block pathologic macrophage-driven neovascularization. We identified the well tolerated and commonly used antibiotic doxycycline as a potent inhibitor of M2-type polarization of macrophages. Doxycycline inhibited, in a dose-dependent manner, M2-type polarization of human and bone marrow-derived mouse macrophages without affecting cell viability. Furthermore, doxycycline inhibited M2-type macrophage polarization and subsequent neovascularization in vivo in a laser injury model of choroidal neovascularization. Thus, doxycycline could be used to enhance current antiangiogenic treatment approaches in various conditions that are promoted by proangiogenic M2-type macrophages, including neovascular age-related macular degeneration and certain cancers. Background: M2-type macrophages are proangiogenic and protumorigenic, whereas M1-type macrophages are antiangiogenic. Results: Doxycycline is a potent inhibitor of M2-type macrophage polarization in both human and mouse macrophages in vitro and in vivo. Conclusion: Preventing M2-type macrophage polarization correlates with inhibition of pathological angiogenesis. Significance: Doxycycline may be used to enhance current antiangiogenic treatment approaches in neovascular age-related macular degeneration and in certain cancers.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Doxycycline Inhibits Polarization of Macrophages to the Proangiogenic M2-type and Subsequent Neovascularization

He, Lizhi ; Marneros, Alexander G.

United States: Elsevier Inc

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