Table 2.
Regulation of CCL2 expression at the maternal-fetal interface.
| Classification | Regulatory factor | Function | Reference |
|---|---|---|---|
| Hormones | E2 | Boosts the production of CCL2 in DSCs by working on the binding sites for AP-1 and NF-kB | (26, 45) |
| Reduces the level of CCL2 in the placenta to control inflammation via ERΑ36/TLR4 pathways | (46) | ||
| HCG | Elevates the level of CCL2 protein and mRNA | (47) | |
| Progesterone | Elevates the level of CCL2 protein and mRNA | (47) | |
| PGF2Α | Increases CCL2 in a dose-dependent manner involving PLC/PKC, ERK1/2, MAPK p38 and PI3K pathway | (48) | |
| VIP | Accelerates the expression of CCL2 to be one of decidualization markers | (49, 50) | |
| Cytokines | IL-33 | Raises the concentration of CCL2 and CCR2 in DSCs through the phosphorylation of NF-kB p65 and ERK1/2 | (51) |
| RANKL | Enhance CCL2/CCR2 axis concerning with NF-kB pathway | (52) | |
| TNF -α | Causes the ascent of CCL2 in first trimester trophoblast cells through the activation of MAPK and c-JNK signaling | (53) | |
| IL-1β | Triggers high expression of CCL2 | (54) | |
| Enzymes and Metabolites | Thrombin | Augments CCL2 protein expression through PAR-1 mediated pathways including PAR-1/Raf-1/MEK/MAPK cascade responses, PAR-1/Rho/Rho-kinase pathway or non-PAR-1 pathway including PLC-InsP3/Ca2+-PKC and downstream ERK1/2 but CCL2 mRNA doesn’t be affected | (55–58) |
| HO-1 | Advances CCL2 and CCR2 expression in decidual cells | (59) | |
| LPA | Works on LPA1 receptor of human first-trimester trophoblast cells and then releases CCL2 via Gi protein, ERK, PKC, p38, Akt, JNK and NF-kB signaling | (60, 61) | |
| Lactate | Restrains the expression of CCL2 via GPR81 | (62) |