IL-1 Family Cytokine Regulation of Vascular Permeability and Angiogenesis

Abstract

The IL-1 family of cytokines are well-known for their primary role in initiating inflammatory responses both in response to and acting as danger signals. It has long been established that IL-1 is capable of simultaneously regulating inflammation and angiogenesis, indeed one of IL-1's earliest names was haemopoeitn-1 due to its pro-angiogenic effects. Other IL-1 family cytokines are also known to have roles in mediating angiogenesis, either directly or indirectly via induction of proangiogenic factors such as VEGF. Of note, some of these family members appear to have directly opposing effects in different tissues and pathologies. Here we will review what is known about how the various IL-1 family members regulate vascular permeability and angiogenic function in a range of different tissues, and describe some of the mechanisms employed to achieve these effects.

Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer

“…The IL-1 family of cytokines (previously hailed as hemopoietin-1) is also implicated in extravasation [71]. Both homologues, IL-1α and IL-1β, were reported to demonstrate angiogenic activities, with IL-1β being able to induce the expression of VEGF [71].…”

“…The IL-1 family of cytokines (previously hailed as hemopoietin-1) is also implicated in extravasation [71]. Both homologues, IL-1α and IL-1β, were reported to demonstrate angiogenic activities, with IL-1β being able to induce the expression of VEGF [71]. IL-1β further induces the expression of both VEGF and VEGFR in a HIF-1α-dependent way, even under normoxia, whereas IL-1α derived from gastric and colonic tumor cells could trigger de novo in vitro [71].…”

The effects of flaxseed and tamoxifen on the inflammatory microenvironment in normal breast tissue and in breast cancer

“…This suggests that the correlation between MVD and IL-1β and IL-1Ra observed in our study may be mediated by VEGF. IL-1β is known to promote angiogenesis via NK-κB activation in TAMs resulting in an increased secretion of VEGF, IL-6 and IL-8 (112). Thus, it would be expected that decreased levels of IL-1β and increased levels of IL-1Ra would reduce the levels of angiogenic factors.…”

“…IL-1s are also known mediators of angiogenesis. In wound healing, this effect seems to be mediated through induction of hypoxia-inducible factor-1α and upregulation of VEGF, whereas in malignancies this seems mainly to be an effect mediated by activated NF-κB in TAMs and the expression of IL-6, IL-8 and adhesion molecules stimulating pro-inflammatory endothelial cells (112). Moreover, in experimental models, inhibition of IL-1β has shown greatly reduced angiogenesis (113,114 increased in intestinal and metabolic diseases and in breast cancer and, has shown to be useful as a biomarker in heart failure (118).…”

The Diverse Roles of TIMP-3: Insights into Degenerative Diseases of the Senescent Retina and Brain

“…VEGF is a key factor in neuropathology, with studies showing that single nucleotide polymorphism in the VEGF promoter region is associated with a risk of AD and vascular dementia [131]. Moreover, the upregulation of the pro-inflammatory cytokine IL-1β has been shown to increase VEGF expression, suggesting a close relationship between inflammation and angiogenesis in AD [132]. In recent years, it has become evident that microglia, the immune cells of the brain, play a key role in the pathogenesis of AD [133].…”