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. 2020 Dec 9;8:600160. doi: 10.3389/fcell.2020.600160

FIGURE 3.

FIGURE 3

Schematic of a selection of the proposed signaling pathways which result from MSC or MSC derived factors interacting with macrophages. (A) The signaling of extracellular vesicles (EV) via negative regulation of the TLR4 (toll-like receptor 4) (Abdi et al., 2018); (B) metabolite signaling via the TCA cycle (Viola et al., 2019); (C) CD200-CD200R1 interaction (Manich et al., 2019); (D) TSG-6 via negative regulation of TLR2 (Choi et al., 2011); (E) AhR via TLR4 signaling (Hinden et al., 2015; Zhu et al., 2018); and (F) PGE2 (Na et al., 2015; Xu et al., 2017). miRNA, microRNA; TLR4, toll-like receptor 4; EV, extracellular vesicle; MyD88, myeloid differentiation primary response 88; IRAK, interleukin-1 receptor-associated kinase; TAK, TGF-β activated kinase; TRAF, TNF receptor-associated factor; p65, NF-κβ p65 subunit; p50, NF-κβ p50 subunit; IKβ, NFKβ inhibitor; NFKβ, nuclear factor kappa light chain enhancer of activated B cells; IL1β, interleukin-1 β; IL-8, interleukin-8; CCL-2, C-C motif chemokine ligand 2; TNFα, tumor necrosis factor α; IL-6, interleukin-6; MSC, mesenchymal stromal cell; HIF1α, hypoxia-inducible factor 1-α; TCA, tricarboxylic acid cycle; ETC, electron transport chain; ATP, adenosine triphosphate; CD200, cluster of differentiation 200; CD200R1, CD200 receptor 1; Crkl, Crk-like protein; Erk, extracellular signal regulated kinase; PI3K, phosphoinositide 3-kinase; TSG-6, TNFα-stimulated gene 6; CD44, cluster of differentiation 44; TLR2, toll-like receptor 2; IKK, inhibitor of nuclear factor NF-κβ kinase, LPS, lipopolysaccharide; AhR, aryl hydrocarbon receptor; Src, proto-oncogene c-Src; Src-P, phosphorylated Src; STAT3, signal transducer and activator of transcription 3; LIF, leukemia inhibitory factor; IL-10, interleukin-10; M-CSF, macrophage colony-stimulating factor; COX-2, cyclooxygenase 2; PGE2, prostaglandin E2; EP4, E-type prostanoid receptor 4; AC, adenylate cyclase; Akt, protein kinase B; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; CREB, cAMP response element binding protein; IL-1RA, interleukin-1 receptor antagonist; CD206 (mannose receptor). Image created with BioRender.