In comparison to wt mice, TCDD-treated AhRR Tg mice had significantly lower expression of CXCL2 and
CXCL3 (Figure 4).
Additionally there also were genes related to the CXC family of chemokines (MCP-1, IL-8, CXCL1, CXCL2,
CXCL3, and CXCR4).
We next matched genes in these three pathways with the 163 genes and identified 12 candidate genes: B-cell CLL/lymphoma 6 (BCL6), IL1[alpha] (ILIA), IL8, PTGS2, DTR, chemokine (C-X-C motif) ligand 3 (
CXCL3), promyelocytic leukemia (PML), sine oculis homeobox homolog 1 (Drosophila) (SIX1), tumor necrosis factor (TNF), [alpha]-induced protein 3 (TNFAIP3), Zn finger and BTB domain containing 1 (ZBTB1), Zn finger protein 44 (KOX 7) (ZNF44), and Zn finger protein 450 (ZNF450).
In castration-resistant prostate cancer from the xenograft mice, release of IL-1[alpha] from the necrotic primary cancer cells results in
CXCL3 secretion, which, in turn, recruits B cells.
The ELR-motif-positive CXC chemokines, CXCL1, CXCL2,
CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8, directly promote the migration and proliferation of endothelial cells and eventually neovascularization, mainly by interacting with CXCR2 but not with CXCR1 [37].
Angiogenic chemokines, such as CXCL1, CXCL2,
CXCL3, CXCL5, CXCL6, and CXCL8, are generally distinguished by an ELR motif.
Additional chemokines are upregulated by LOX-1 activation in response to OxLDL, including IL-8, chemokine (CX-C motif) ligands 2 and 3 (CXCL2 and
CXCL3) [19].
OxLDL administration was also shown to induce the production of IL-6 from HUVECs [20], chemokines CXCL2 and
CXCL3 from LOX-1 overexpressing human aortic endothelial cell line [35], MCP-1 from human articular chondrocytes [36], and the intestinal tissue of animals with endotoxemia [1].