{
  "abstract": "Background Oestrogen plays a regulatory role in tissue homeostasis. Following menopause, oestrogen levels decline, which may reduce protective signalling through oestrogen receptors. In COPD, postmenopausal women experience greater symptom burden, while men display more emphysema (1). Fibroblasts are involved in both inflammation and remodelling. Oestrogen receptor beta (ER-β), encoded by ESR2, is expressed in the lung and may influence sex-specific airway pathology (2). We hypothesised that oestrogen modulates inflammatory and matrix-related responses via ER-β in a sex-specific manner.Methods Small airway fibroblasts (SAFs) were isolated from COPD patients undergoing lung resection (n = 17; 9 women) and treated with oestrogen (10 − 1 2 to 10− 6 M), PPT (ER-α agonist), or DPN (ER-β agonist), ± IL-1β. CXCL8 release was measured by ELISA. Expression of oestrogen receptor alpha (ESR1) and oestrogen receptor beta (ESR2) mRNA was quantified by RT-qPCR in SAFs. Lung tissue (n = 33; 13 women) was analysed for ESR1, ESR2, matrix metalloproteinases (MMP9, MMP2), and collagens (COL1A1, COL3A1, COL4A1). Among women donors, all were postmenopausal and not on hormone therapy; mean age was 71 years (range 59–77) and BMI 25.8 (18.5–29.6). Men had a mean age of 67 years (range 45–81) and BMI 26.4 (21.5–31.5).Results In SAFs, oestrogen reduced IL-1β-induced CXCL8 release in a concentration-dependent manner (maximally at 10 − 9 M, p = 0.0077). DPN reduced CXCL8 by 46.9% (p = 0.00047), while PPT had no effect. SAFs expressed approximately twofold higher ESR2 than ESR1. In lung tissue, ESR2 expression was higher in women. A moderate correlation between ESR2 and MMP9 was observed in men (r = 0.42, p = 0.097), but not in women (r = 0.05, p = 0.86). Other matrix-related genes and collagens did not show significant sex-based variation.Conclusion Our results suggest that ER-β is the predominant oestrogen receptor in airway fibroblasts and reduces CXCL8 release. These findings support ER-β as a context-dependent modulator of COPD. Further research is needed to clarify ER-β’s regulatory mechanisms relevance to sex-specific airway inflammation and remodelling.",
  "authors": [
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "C Mwasuku"
    },
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "J Baker"
    },
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "L Rose"
    },
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "M Bafadhel"
    }
  ],
  "title": "S122 Oestrogen and ER-β: implications for COPD",
  "uid": "7f80f10d-5577-5145-8bee-11349ececf6f"
}