Table 1.
S1P/S1PRs signaling and monocyte/macrophage function under inflammatory and pathological conditions.
| Inflammatory Conditions | Signaling Pathways |
S1P Receptors | Roles |
|---|---|---|---|
| Palatal wound healing [57] | MCP-1, HIF-1α, MIP-1α, iNOS, TNF-α, Akt, p38 | S1P1 | Infiltration of M1/M2 macrophages |
| CNS autoimmunity and neuroinflammation [41] | STAT-3, JAK, IL-6 | S1P1 | Pronounced activation of monocytes |
| Inflammation and atherosclerosis [21,24,25,31,32,33] | TNF-α, MCP-1, IL-6, Akt, PI3K, PKC, ERK1/2, p38, Rho kinases | S1P1 | Activation and migration of macrophages |
| Gα12/13, NF-κB, RhoA | S1P2 | Inhibits macrophage migration (negative effect) and inhibits M1 activation | |
| MCP-1, TNF-α, Sphk1 | S1P3 | Migration of monocytes/macrophages | |
| Tubulointerstitial inflammation [36] | MCP-1, SphK1, TNF-α, arginase-1, IL-6, IL-10 | S1P1 S1P3 |
Macrophage infiltration |
| Acute allergic [37] | MCP-1/CCL2, MIP-1α, RANTES/CCL5 | S1P2 | Macrophage infiltration |
| Inflammation and liver injury [29,30,179] | Gαi/o, PI3K, JNK, Rac1 | S1P2 S1P3 |
Migration of BMMs, M1 polarization |
| NLRP3, IL-1β, IL-18, p38, ERK, JNK, Gα12/13 | S1P2 | Blockade BMMs activation and M1 polarization | |
| Rheumatoid arthritis [23,175] | NF-κB, Fas, Akt, p38, ERK1/2, Rac, Rho | S1P1 | Motility and number of BMMs induced osteoclast |
| Cerebral ischemia [49] | NF-κB p65, ERK1/2, p38, Akt | S1P3 | M1 polarization |
| Bacterial sepsis [50,173,177] | Caspase-11 | S1P2 | Macrophage pyroptosis |
| MCP-1, Sphk1, TNF-α, arginase-1, IL-6, IL-10 | S1P1 S1P3 |
Macrophage infiltration | |
| Psoriasis [54] | IL-6, CCL2, CXCL1 | S1P4 | M2 macrophage infiltration |
| Bone marrow sinusoidal inflammation [55] | CCR2 | S1P5 | Monocyte migration |
| Pulmonary disease [27,28] | CCR2 | S1P5 | Monocyte migration |
| Encephalomyelitis [25] | CCR2 | S1P5 | Inflammatory monocytes supply the concentration of lymph node S1P |
Several inflammatory conditions related to monocyte/macrophage disturbances (wound healing, allergies, liver injury, and arterial/pulmonary diseases) are a hallmark feature of hypoxia and are detected by S1P/S1PR signaling. These disturbances are related to various cellular signaling pathways that mediate cell survival, migration, and apoptosis. S1P1–3 contribute to the activation, motility, and infiltration of monocytes/macrophages. Meanwhile, S1P4–5 only contribute to the migration and infiltration of monocytes/macrophages. However, supporting research remains to be further analyzed. Thus, activation of S1P/S1PRs in monocytes/macrophages through various pathways can trigger functional responses as indicated. Targeting of the genes indicated may therefore be of interest in disease settings.