Regulatory role of local tissue signal Del-1 in cancer and inflammation: a review

Abstract

Developmental endothelial locus-1 (Del-1) is a secretory, multifunctional domain protein. It can bind to integrins and phosphatidylserine. As a local tissue signal, it plays a regulatory role in the cancer microenvironment and inflammation. Del-1 has destructive effects in most cancers and is associated with the progression and invasion of some cancers. In contrast, Del-1 also plays a protective role in inflammation. Del-1 regulates inflammation by regulating the generation of neutrophils in bone marrow, inhibiting the recruitment and migration of neutrophils and accelerating the clearance of neutrophils by macrophages. Del-1 and IL-17 are reciprocally regulated, and their balance maintains immune system homeostasis. Del-1 is expected to become a new therapeutic target for inflammatory disorders such as multiple sclerosis.

Metabolomics Profiling of Tunisian Sonchus oleraceus L. Extracts and Their Antioxidant Activities

“…As mentioned in several studies, polyphenols, flavonoids and tannins are efficient scavengers against oxidative stress, and free radicals [46,47] …”

“…In fact, the presence of a hydroxy group on the benzene ring by mean of the hydrogen atom transfer (HAT) all with the single electron transfer (SET), is essentially responsible for generating harmless species, and oxidised, less reactive radicals [54] . Since antioxidants are present in nature rather in mixture of different classes, than isolated compounds, therefore, their activity is more likely the result of an additive effect, not mentioning the fact that polyphenols are multifunctional themselves and can interact in so many biological reactions [10–55] …”

Variants Within Genes EDIL3 and ADGRB3 are Associated With Divergent Fecal Egg Counts in Katahdin Sheep at Weaning

“…The gene EDIL3 encodes the protein epidermal growth factor (EGF)-like repeat and discoidin I-like domain-containing protein 3, a secreted glycoprotein which acts as an integrin ligand and has non-redundant roles in multiple stages of the immune response, including myelopoiesis, anti-inflammatory regulation of neutrophil infiltration and resolution of inflammation ( Mitroulis et al, 2017 ; Chen et al, 2018 ; Hajishengallis and Chavakis 2019 ; Li et al, 2021 ). Endothelial cells secrete EDIL3 to limit neutrophil recruitment to sites of infection and restrain the initiation of inflammation.…”

“…This is accomplished by interfering with the interaction of lymphocyte function-associated antigen-1 (LFA-1) integrin on leukocytes with intercellular adhesin molecule-1 (ICAM-1) on the surface of vascular endothelial cells ( Shin et al, 2013 ; Li et al, 2021 ). It is also thought to inhibit ICAM-1-dependent chemokine release (CXCL2 and CCL3) by neutrophils, and EDIL3 is thought to be involved in downstream processes of inflammation through binding to the αvβ3 integrin on the macrophage and phosphatidylserine on the apoptotic neutrophil cell to mediate efferocytosis and inflammation resolution ( Hanayama et al, 2004 ; Kourtzelis et al, 2019 ; Li et al, 2021 ). EDIL3 is reciprocally regulated with the proinflammatory cytokine IL-17 ( Shin et al, 2013 ; Choi et al, 2015 ; Yan et al, 2018 ; Li et al, 2021 ).…”

“…It is also thought to inhibit ICAM-1-dependent chemokine release (CXCL2 and CCL3) by neutrophils, and EDIL3 is thought to be involved in downstream processes of inflammation through binding to the αvβ3 integrin on the macrophage and phosphatidylserine on the apoptotic neutrophil cell to mediate efferocytosis and inflammation resolution ( Hanayama et al, 2004 ; Kourtzelis et al, 2019 ; Li et al, 2021 ). EDIL3 is reciprocally regulated with the proinflammatory cytokine IL-17 ( Shin et al, 2013 ; Choi et al, 2015 ; Yan et al, 2018 ; Li et al, 2021 ). IL-17 is produced by Th17 cells to promote recruitment of macrophages and neutrophils to aggravate chronic inflammation ( McRae et al, 2015 ; Sehrawat and Rouse, 2017 ).…”