Figure legends:
Figure 1: Regulation of DEL-1 expression. IL-17 and TNF reduces DEL-1 expression in a GSK3β-dependent process that inhibits the binding of the key transcription factor C/EBPβ to the EDIL3 promoter, thereby downregulating EDIL3 transcription. This inhibitory action of IL-17 can be reversed at the GSK-3β level by PI3K/Akt signalling induced by D-resolvins. Through interaction with GHSR, ERM activates JAK2 signaling, leading to DEL-1 transcription, which is MAPK p38-mediated and C/EBPβ-dependent, as well as to PI3K/AKT-mediated reversal of the GSK3β-dependent inhibitory effect of IL-17 on DEL-1 expression. DHEA reduced DEL-1 expression and secretion in endothelial cells by activating TRKA and downstream PI3K/AKT signaling to restore C/EBPβ binding to the DEL-1 promoter. In addition, P53 overexpression and the activation of P38/MK2 signaling were reported to promote DEL-1 expression. DEL-1, Developmental endothelial locus-1; GSK-3β, glycogen synthase kinase 3β; C/EBPβ, CCAAT/enhancer-binding protein β; PI3K, phosphoinositide 3-kinase; MAPK, mitogen-activated protein kinases; GHSR, growth hormone secretagogue receptor; ERM, erythromycin; JAK2, janus kinase 2; DHEA, dehydroepiandrosterone; TRKA, tropomyosin receptor kinase A.
Figure 2: Structure and biological roles of DEL-1. Shown are the multi-domain structure of DEL-1 as well as six major regulatory activities of this protein, namely promoting myelopoiesis, inhibiting neutrophil recruitment, promoting efferocytosis, modulating Tregs, promoting angiogenesis and inhibiting fibrosis. DEL-1, Developmental endothelial locus-1; ECM, extracellular matrix; HSC, hematopoietic stem cell; MyP, myeloid progenitors; ICAM-1, intercellular adhesion molecule-1; LFA-1, lymphocyte function-associated antigen-1; PS, phosphatidyl serine; Th17, T helper 17 cell; Treg, T regulatory cell; FOXP3, forkhead box P3; HoxD3, Homeobox D3; MMP2, matrix metallopeptidase 2; LPA, latency-associated peptide; TGF-β, transforming growth factor-β.