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Departments of
*
Medical Biochemistry and
Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan
IL-13 is a multifunctional lymphokine sharing a number of
biological properties with IL-4. We previously observed that IL-4 shows
angiogenic activities in vitro as well as in vivo. In this study we
examined the effect of IL-13 on angiogenesis in vitro and in vivo and
also the underlying mechanisms. Human IL-13 significantly stimulated
the formation of tube-like structures in collagen gels by human
microvascular endothelial cells and bovine aortic endothelial cells by
about 3-fold over the controls in the absence of the cytokines.
Administration of murine IL-13 led to neovascularization when implanted
in the rat cornea. Coadministration of neutralizing mAb to the IL-4R
inhibited both tubular morphogenesis in vitro and activation of STAT6
induced by IL-4 or IL-13. Both IL-4 and IL-13 markedly increased mRNA
levels of VCAM-1 in vascular endothelial cells, and the production of
the soluble form of VCAM-1 was also stimulated in response to IL-4 or
IL-13. Administration of anti-VCAM-1 Ab in vitro blocked tubular
morphogenesis induced by IL-4 and IL-13. Angiogenesis induced in vivo
in rat cornea by IL-4 and IL-13 was also inhibited by Ab against the
rat 
4 integrin subunit. These findings suggest that
angiogenesis dependent on IL-4 and IL-13 is mainly mediated through a
soluble VCAM-1/4 integrin
pathway.
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