The role of IL-1β in the early tumor cell-induced angiogenic response.

In this study, we assessed the involvement of IL-1β in early angiogenic responses induced by malignant cells using Matrigel plugs supplemented with B16 melanoma cells. We found that during the angiogenic response, IL-1β and vascular endothelial growth factor (VEGF) interact in a newly described autoinduction circuit, in which each of these cytokines induces the other. The IL-1β and VEGF circuit acts through interactions between bone marrow-derived VEGF receptor 1(+)/IL-1R1(+) immature myeloid cells and tissue endothelial cells.

IL-1α and IL-1β recruit different myeloid cells and promote different stages of sterile inflammation.

The immune system has evolved to protect the host from invading pathogens and to maintain tissue homeostasis. Although the inflammatory process involving pathogens is well documented, the intrinsic compounds that initiate sterile inflammation and how its progression is mediated are still not clear. Because tissue injury is usually associated with ischemia and the accompanied hypoxia, the microenvironment of various pathologies involves anaerobic metabolites and products of necrotic cells.

Reduced atherosclerosis and inflammatory cytokines in apolipoprotein-E-deficient mice lacking bone marrow-derived interleukin-1α.

Objective: Interleukin (IL)-1α and IL-1β are products of macrophages, endothelial cells and vascular smooth muscle cells; moreover, each of these cell types is affected by the pro-inflammatory properties of both IL-1's. Whereas several studies demonstrate the proatherogenic properties of IL-1β, the role of IL-1α in atherogenesis remains unclear. We assessed whether IL-1α and IL-1β from tissue resident vascular cells or emigrating bone marrow-derived cells promote the development of atherosclerosis in apoE-/- mice and determined the effect of selective macrophage IL-1α or IL-1β deficiency on degradation of LDL and cytokine production.

Differential release of chromatin-bound IL-1alpha discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation.

IL-1alpha, like IL-1beta, possesses multiple inflammatory and immune properties. However, unlike IL-1beta, the cytokine is present intracellularly in healthy tissues and is not actively secreted. Rather, IL-1alpha translocates to the nucleus and participates in transcription.

The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis.

Inflammation and angiogenesis are pivotal processes in the progression of many diseases, including malignancies. A hypoxic microenvironment often results in a milieu of proinflammatory and proangiogenic cytokines produced by infiltrating cells. We assessed the role of macrophage-derived hypoxia-associated cytokines in promoting inflammation and angiogenesis.

Host-derived interleukin-1alpha is important in determining the immunogenicity of 3-methylcholantrene tumor cells.

Using IL-1/IL-1Ra knockout BALB/c mice, we showed that 3-methylcholatrene (3-MCA)-induced carcinogenesis is dependent on IL-1beta-induced inflammatory responses. Patterns of local inflammation and tumorigenicity were similar in wild-type (WT) and IL-1alpha(-/-) mice, while in IL-1beta(-/-) mice, tumorigenicity was attenuated and in IL-1Ra(-/-) mice accentuated. 3-MCA-induced fibrosarcoma cell lines from WT mice developed into progressive tumors in WT mice, while surprisingly, lines from IL-1alpha(-/-) mice formed tumors only in immunocompromized mice.

The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions.

Interleukin-1 (IL-1) includes a family of closely related genes; the two major agonistic proteins, IL-1alpha and IL-1beta, are pleiotropic and affect mainly inflammation, immunity and hemopoiesis. The IL-1Ra antagonist is a physiological inhibitor of pre-formed IL-1. Recombinant IL-1alpha and IL-1beta bind to the same receptors and induce the same biological functions.