{
  "abstract": "Background Chronic Obstructive Pulmonary Disease (COPD) is associated with persistent airway inflammation, which may be driven by an imbalance between pro-inflammatory macrophages and dysfunctional anti-inflammatory macrophages. Resolvin D1 (RvD1), is a specialised pro-resolving mediator derived from the breakdown of docosahexaenoic acid by arachidonate 15-lipoxygenase (ALOX15). RvD1’s role on macrophage function is poorly understood.Objective 1 To investigate the effect of RvD1 on the phagocytic activity and inflammatory cytokine response of COPD monocyte-derived macrophages (MDMs) to Haemophilus Influenzae (HI).Objective 2 To establish the relationship between RvD1 signalling and anti-inflammatory IL-10 production via STAT3.Methods Peripheral blood monocytes were derived from COPD patients (n=10) and then cultured in GM-CSF/M-CSF respectively for 12 days to generate pro/anti-inflammatory G-MDMs/M-MDMs. MDMs were treated with vehicle (EtOH) or exogenous 1nM/10nM RvD1 30 minutes prior to and 1-hour post-exposure to fluorescently labelled HI. Phagocytosis was measured using FLUOstar OPTIMA at 4h and 24h, and values corrected using MTT assay for cell viability. Supernatants and cell-lysates were collected at 0, 4h and 24h for ELISA, qPCR and western blot.Results There was no improvement in the phagocytic activity of RvD1 treated MDMs compared to vehicle in both G-MDMs and M-MDMs. In M-MDMs, 10nM RvD1 treatment compared to vehicle resulted in a significant reduction in both IL-6 (452.5 vs 171.1 pg/mL, p= 0.0197) and CXCL8 (923.8 vs 853.9 pg/mL, p= 0.0186) at 24 hours. RvD1 also increased production of IL-10 (150.8 vs 418.9, p=0.0523). Interestingly, this corresponded to a 2-fold increase in STAT3. Further, HI infected cells showed 1.5-fold increase in RvD1 receptor (FPR2) expression at 24 hours, compared to vehicle. There was also increased expression of ALOX15 in the vehicle group at 4h compared to the RvD1 treated group (1.1 vs 0.8 fold change, p=0.044).Conclusion RvD1 ameliorated the inflammatory cytokine response to HI in COPD M-MDMs with greatest effects seen at 24h. ALOX15 is involved in synthesis of RvD1 during the early stages of bacterial infection in COPD MDMs, which may explain why patients with viral AECOPD experience worse symptoms and delayed recovery. Work is ongoing to determine the effects of RvD1 on virus-infected MDMs.",
  "authors": [
    {
      "affiliations": [
        "Imperial College London, London, UK"
      ],
      "name": "J Mah"
    },
    {
      "affiliations": [
        "Imperial College London, London, UK"
      ],
      "name": "P Fenwick"
    },
    {
      "affiliations": [
        "Imperial College London, London, UK"
      ],
      "name": "R Lopez"
    },
    {
      "affiliations": [
        "Imperial College London, London, UK"
      ],
      "name": "Y Guo"
    },
    {
      "affiliations": [
        "Imperial College London, London, UK"
      ],
      "name": "F Shrosbery"
    },
    {
      "affiliations": [
        "Imperial College London, London, UK"
      ],
      "name": "SWJ Bartlett-Pestell"
    },
    {
      "affiliations": [
        "Imperial College London, London, UK"
      ],
      "name": "A Braddy-Green"
    },
    {
      "affiliations": [
        "Imperial College London, London, UK"
      ],
      "name": "J Devulder"
    },
    {
      "affiliations": [
        "Imperial College London, London, UK"
      ],
      "name": "RJ Snelgrove"
    },
    {
      "affiliations": [
        "Imperial College London, London, UK"
      ],
      "name": "L Donnelly"
    },
    {
      "affiliations": [
        "Imperial College London, London, UK"
      ],
      "name": "JA Wedzicha"
    },
    {
      "affiliations": [
        "Imperial College London, London, UK"
      ],
      "name": "LJ Finney"
    }
  ],
  "title": "S60 Resolvin D1 ameliorates the inflammatory response to haemophilus influenzae infection in COPD monocyte-derived macrophages",
  "uid": "d4817467-5d53-58e0-ae19-f907a6db0877"
}