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.