{
  "abstract": "Background The polymorphisms of ORMDL3 on human chromosome strongly associate childhood asthma and asthma exacerbations. It has multiple functions in human epithelial cells, regulating de novo sphingolipid synthesis, protein folding, glycolysis, and the expression of the human rhinovirus (HRV) receptor intercellular adhesion molecule 1 (ICAM-1), which increases HRV infection. This is known to be a major exacerbator of asthma. We previously found ORMDL3 influencing the expression of the ferroptosis gene HMOX1. In this research, we investigate HMOX1 levels in ORMDL3 knockout and overexpression cells.Methods ORMDL3 knockout cells were generated by applying CRISPR/Cas9 techniques in HBEC3-KT epithelial cells. ORMDL3 knockdown cells were established by applying ORMDL3 siRNAs in A549 epithelial cells. ORMDL3 overexpression plasmids were used to generate an overexpression model in HBEC3-KT cells. Cells were stimulated with LPS/IL-13 or erastin to induce ferroptosis in epithelial cells, ferroptosis-associated genes GPX4, SLC7A11, HMOX1, DHODH, ACSL4, and ACSL3 were quantified by qPCR, and GPX4, SLC7A11, and HMOX1 were analysed by immunofluorescent staining and Western blotting. IL-6 and IL-8 levels from cell supernatants were examined with ELISA.Results In ORMDL3 knockdown A549 cells, the transcript levels of HMOX1 were lower, whereas in ORMDL3 overexpression HBEC3-KT cells, the transcript levels of HMOX1 were higher. ORMDL3 overexpression showed lower GPX4 and SCL7A11 levels in immunofluorescent staining after inducing by LPS/IL-13. The ongoing work included examining transcript levels of HMOX1 in ORMDL3 knockout cells and GPX4, SCL7A11, HMOX1 levels in ORMDL3 overexpression cells and ORMDL3 knockout cells treated with erastin.Conclusions ORMDL3 regulates ferroptosis in human epithelial cells. It regulates ferroptosis gene HMOX1 levels. Our results provide new insights into ferroptosis in asthma and may identify potential targets for childhood asthma and asthma exacerbations.",
  "authors": [
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "S Chi"
    },
    {
      "affiliations": [
        "Department of Surgery and Cancer, Imperial College London, London, UK"
      ],
      "name": "H Zhao"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "J Weinman"
    },
    {
      "affiliations": [
        "Department of Surgery and Cancer, Imperial College London, London, UK"
      ],
      "name": "D Ma"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "K Ito"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "WO Cookson"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "MF Moffatt"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "Y Zhang"
    }
  ],
  "title": "P248 ORMDL3 influences ferroptosis through HMOX1 in human bronchial epithelial cells",
  "uid": "437184f7-caa8-5a3b-acf7-164ff6728ca3"
}