{
  "abstract": "Background Polymorphisms on human chromosome 17q21 confer the major genetic susceptibility to childhood-onset asthma. The loci consist of ORMDL3 and GSDMB genes. The risk alleles positively correlate with both genes’ expression. ORMDL3 has been extensively studies and showed it regulates many pathways and human rhinovirus (HRV) infection in cell inflammation, but GSDMB’s role in human rhinovirus infection and asthma exacerbation are incompletely understood.Methods GSDMB knockouts in human airway epithelial HBEC3-KT cells were created by CRISPR/Cas9 techniques. The knockout cells were challenged by IL-1β, TNF-α, Poly IC, LPS and human rhinovirus HRV16. Cytokine levels of IL-6 and IL-8 from supernatants were examined by ELISA, viral loading was checked by resazurin assay and viral copies were measured by qPCR. GSDMB overexpression epithelial cells were established in HBEC3-KT cells. Cytokine levels in time course treatment were analysed by ANOVA. Transcript abundances were analysed by qPCR.Results Human rhino virus infected to the GSDMB knockout cells to show reduced inflammatory response and viral loading. GSDMB overexpression cells augmented inflammatory response after HRV infection. Poly I:C, a synthetic double-stranded RNA (dsRNA) of virus, stimulated knockout cells showed dramatically reduction of levels of IL-6 and IL-8. Knockout cells showed differently to release IL-6 and IL-8 with different stimulators.Conclusions Our results show GSDMB has important role in epithelial cells in viral infection. Consistent with its substantial genetic influence on childhood asthma. Actions on GSDMB provide a potential mechanism for the locus to confer susceptibility to HRV-induced asthma.",
  "authors": [
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "H Du"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "J Ma"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "M Lei"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "H Guo"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "L Daly"
    },
    {
      "affiliations": [
        "The Department of Surgery and Cancer, Imperial College London, London, UK"
      ],
      "name": "E Zhang"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "M Wang"
    },
    {
      "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": "P250 GSDMB regulates human rhinovirus replication and inflammation in airway epithelial cells",
  "uid": "33dc52d2-0e61-501e-a037-b1ae6bb14b96"
}