Table 3.
Bioactions of SPMs on cytokine secretion and leukocytes activity, demonstrated in non-CF models.
| Cytokines synthesis /Leukocytes activity | ||||
|---|---|---|---|---|
| Conditions | SPMs | Models | Bioactions | References |
| In vitro studies | ||||
| TNF-α treatment | LXA4 | Human umbilical vein endothelial cells | Up-regulates miR-126-5p (related to endothelial repair and VCAM-1 expression) | Codagnone et al., 2017 |
| LXA4 and AT-LXA4 analog | Human peripheral blood PMNs | Inhibit TNF-α-initiated neutrophil migration, superoxide generation and IL-1β release | Hachicha et al., 1999 | |
| TGF-β1-induced fibrosis | LXA4 | Human renal epithelial HK-2 cell line Human mesangial cells Rat renal fibroblast cells (NRK49F) |
Up-regulates miR let-7c (reduces renal fibrosis) in human cells Decreases miR let-7c level in rat cells |
Brennan et al., 2013 |
| Intestinal Salmonella Typhimurium | LXA4 analog | Human intestinal epithelium T84 cell line | Inhibits IL-8 secretion | Gewirtz et al., 1998 |
| Airway P. aeruginosa | AT-LXA4 analog | Human primary bronchial epithelial cells | Inhibits IL-8 secretion | Karp et al., 2004 |
| Chemoattractant | LXA4 | Human peripheral blood PMNs | Inhibits LTB4/FMLP-induced PMN chemotaxis and migration | Lee et al., 1989 |
| LXA4, LXB4 | Human peripheral blood PMNs, HUVEC | Inhibit LTB4-induced PMN adhesion to endothelial cells and migration across endothelial cell monolayers | Papayianni et al., 1996 | |
| LXA4 analog | Human peripheral blood PMNs, HL-60 cells, HUVEC | Inhibit PMN transendothelial migration and endothelial adhesion | Serhan et al., 1995 | |
| RvD1, AT-RvD1 | Human peripheral blood PMNs and microvascular endothelial cells (HMEC-1) | Inhibit PMN transendothelial migration | Sun et al., 2007 | |
| RvE3 | Human peripheral blood PMNs | Inhibits PMN chemotaxis | Isobe et al., 2012 | |
| Acid lung injury | LXA4 | Human bronchial epithelial (HBE) and type II alveolar (A549) cell lines | Inhibits IL-6 release and PMN transendothelial migration | Bonnans et al., 2006 |
| Asthma | LXA4, LXB4 | Human asthmatic peripheral blood mononuclear cells | Inhibit IL-8 release | Bonnans et al., 2002 |
| Cigarette smoke | RvD1, RvD2 | Human peripheral blood monocytes and alveolar macrophages | Decrease release of pro-inflammatory cytokines (IL-6, IL-8 and TNF-α) and increase release of IL-10 and TGF-β Stimulate phagocytosis and M2 state Decrease levels of protein carbonylation after 24h |
Croasdell et al., 2015 |
| RvE1 | Murine macrophage RAW264.7cell line | Stimulates phagocytic activity and reduces cell death | Takamiya et al., 2012 | |
| RvD1 | Human bronchial epithelial 16HBE cell line | Reduces IL8 synthesis | Jiajia et al., 2014 | |
| AT-RvD1 | Human THP1 macrophages and alveolar epithelial A549 cell lines | Reduces IL-1β secretion in macrophages and IL-6 and IL-8 secretion in alveolar cells | Cox et al., 2015 | |
| Polyinosinic-polycytidylic acid | RvD1 | Human primary lung epithelial cells | Inhibits IL-6 and IL-8 release | Hsiao et al., 2014 |
| Microbial sepsis | RvD2 analog | Human primary PMNs and HUVEC | Stimulates NO production in HUVEC Reduces L-selectin and CD-18 surface expression Stimulates phagocytosis of E. Coli Increases intracellular ROS |
Spite et al., 2009 |
| E. Coli | RvD1 analog, RvD5 analog, PD1 |
Human peripheral blood monocyte and PMN | Increase phagocytosis of E. Coli (RvD1,RvD5, PD1) Regulate inflammatory genes (RvD1, RvD5) |
Chiang et al., 2012 |
| Mar1, 22-OH-MaR1, 14-oxo-MaR1 | Human primary peripheral blood macrophages | Increase macrophage phagocytosis | Colas et al., 2016 | |
| PMA/Ionomycin | RvD1, RvD2, AT-RvD3 MaR1 | Human peripheral blood CD8+ and CD4+ T cells | Inhibit TNF-α, IFN-γ, IL-2 production Favor CD+4 T cells differentiation into regulatory T cells Inhibit naive CD+4 T cells differentiation into TH1 and TH17 cells |
Chiurchiù et al., 2016 |
| Other | RvE1, RvD1, RVD2, PD1 |
Human peripheral blood mononuclear cells | RvD1 regulates miR-146b, miR-21, miR-208 and miR-219-5p RvE1 regulates miR-219-5p and miR-21 but not miR146b RvD2 and PD1 regulate miR-146b and miR-21 but not miR-219-5p |
Fredman et al., 2012 |
| PDn-3 DPA | Human peripheral blood macrophages | Regulates monocyte-to-macrophage differentiation | Pistorius et al., 2018 | |
| Sickle-cell disease (SCD) | AT-RvD1 and RvD1 | Human endothelial cell line, human SCD blood PMN and erythrocytes | Inhibit neutrophil recruitment Stimulate erythrocytes and PMN efferocytosis |
Matte et al., 2019 |
| In vivo studies | ||||
| TNF-α | LXA4 and AT-LXA4 analog | BALB/c mice | Inhibit leukocyte infiltration | Hachicha et al., 1999 |
| Chronic renal fibrosis | LXA4 | Male wistar rats | Up-regulates miR let-7c (reduces renal fibrosis) | Brennan et al., 2013 |
| LPS-induced lung injury | LXA4, RvD1 | Male Sprague-Dawley rats (BAL) | Reduce TNF-α, IL-6 and IL-1β secretion Increase IL-10 secretion |
Wang Q. et al., 2014, Yang et al., 2013 |
| Acute peritonitis | RvD1, AT-RvD1 | Male FVB mice | Reduce leukocyte infiltration | Sun et al., 2007 |
| RvD1 | C57Bl/6N mice | Reduces leukocytes infiltration Stimulates M2 differentiation and activity Regulates corresponding genes |
Recchiuti et al., 2014 | |
| RvD1 analog | Male FVB mice | Temporally controls miRNAs: at 12h, increases miR21 and miR146b, decreases miR208a (NF-kB signaling) and miR219 (LTB4 production) | Recchiuti et al., 2011 | |
| RvE3 | Male FVB mice | Inhibits PMN infiltration | Isobe et al., 2012 | |
| Asthma | RvE1 | Female BALB/c mice | Lowers mucus score | Aoki et al., 2008 |
| Microbial sepsis | RvD2 analog | Male FVB mice, eNOS-/- & wild type (C57BL/6J) mice | Reduces neutrophils recruitment, leukocyte-endothelial interactions (NO-dependent) Reduces local and systemic bacterial burden Increases peritoneal mononuclear cells Increases survival Reduces IL-6, IL-1β, IL-23, TNF-α |
Spite et al., 2009 |
| Peritoneal E. Coli & Skin S. aureus | RvD1 analog, RvD5 analog, PD1 |
Male FVB mice, C57BL/6J male mice | Reduces bacterial burden in blood and exudates (RvD1, RvD5) Increase survival (RvD1, RvD5) Amplify antimicrobial response of ciprofloxacin Increase clearance of S. aureus with vancomycin Reduce IL-1β, IL-6 and increase IL-10 secretion (RvD1) Reduce KC and TNF-α secretion (RvD5) |
Chiang et al., 2012 |
| Peritoneal E. Coli | PDn-3 DPA | Male C57Bl/6N mice | Increases macrophages' efferocytosis and bacterial phagocytosis | Pistorius et al., 2018 |
| Sickle-cell disease (SCD) | AT-RvD1 | SCD and healthy (Hbatm1(HBA)Tow Hbbtm3(HBG1, HBB)Tow) mice |
Reduces neutrophils adhesion & transmigration Reduces lung and kidney injury Reduces proinflammatory cytokine |
Matte et al., 2019 |