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. 2013 Dec 24;3:9–18. doi: 10.2147/ITT.S32049

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© 2014 Rolin and Maghazachi. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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Interactions among chemokines and inflammatory lipids.

Notes: Both chemokines and inflammatory lipids receptors are coupled to G proteins. S1P1 binds S1P_1–5, FTY720 binds S1P_1,3,4,5, and PEG2 binds EP2 and EP4. Activity 1: CCR2, CCR5, and CCR7, as well as CXCR4 and CXCR5, contribute to the effect of FTY720-induced homing of lymphocytes. Activity 2: FTY720 through S1P receptor agonism reduced the expression of CCR1, CCR2, and CCR5 in renal parenchyma. Activity 3: Overexpression of S1P₁ inhibits the migratory effect of CXCL12/SDF-1α for peripheral blood progenitor cells, and this effect is reduced upon FTY720 treatment due to downregulation of S1P₁. Activity 4: The expression of CXCR4, as well as the secretion of CXCL12/SDF-1α, is increased by PGE2 on myeloid derived suppressor cells, leading to their recruitment into tumor growth sites. Activity 5: PGE2 is a prerequisite for the expression of CCR7 in monocyte derived DCs, and it enhances their migration towards lymph node associated chemokines CCL19/MIP-3β or CCL21/MIP-3α. However, the expression of CCR5 and CXCR3 in monocytes and macrophages is blocked, impeding natural killer cell-DC’s cross talk.

Abbreviations: PGE2, Prostaglandin E2; EP, prostaglandin E receptor; DCs, dendritic cells; CCR, CC chemokine receptor; CXCR, CXC chemokine receptor; SDF, stromal cell-derived factor; MDSCs, myeloid derived supressor cells; PBPCs, peripheral blood progenitor cells; S1P, sphingosine 1-phosphate.