IL-32 promotes angiogenesis.

Area of Science:

• Immunology
• Cell Biology
• Vascular Biology

Background:

• Interleukin-32 (IL-32) is a pleiotropic cytokine involved in inflammation, immunity, and cancer.
• Previous work identified IL-32 as a regulator of endothelial cell (EC) functions.
• Increased IL-32 expression is observed in hyperproliferative ECs in pulmonary arterial hypertension and glioblastoma.

Purpose of the Study:

• To investigate the role of IL-32 in endothelial cell proliferation and angiogenesis.
• To determine the mechanisms underlying IL-32's angiogenic properties, including its interaction with integrin αVβ3 and dependence on VEGF.

Main Methods:

• Small interfering RNA (siRNA) to silence IL-32 expression in endothelial cells.
• Coculture angiogenesis assays and in vivo matrigel plug assays in mice.
• Analysis of EC proliferation, apoptosis markers, nitric oxide (NO), cytokine, and matrix metalloproteinase levels.
• Use of integrin αVβ3 inhibitors and investigation of cofactor requirements (e.g., IFN-γ).

Main Results:

• Silencing IL-32 significantly reduced EC proliferation and altered the production of NO, IL-8, matrix metalloproteinase-9, activin A, and endostatin.
• IL-32γ dose-dependently promoted tube formation in vitro and exhibited potent angiogenic activity in vivo, comparable to VEGF.
• IL-32's angiogenic effects were mediated by integrin αVβ3, independent of VEGF, and required a secondary signal like IFN-γ for full responsiveness.

Conclusions:

• IL-32 possesses significant angiogenic properties, mediated via integrin αVβ3 and independent of VEGF.
• These findings reveal a novel role for IL-32 in vascular remodeling and implicate it in pathological angiogenesis associated with diseases like pulmonary arterial hypertension and cancer.