2021
Machine learning implicates the IL-18 signaling axis in severe asthma
Camiolo MJ, Zhou X, Wei Q, Bittar H, Kaminski N, Ray A, Wenzel S. Machine learning implicates the IL-18 signaling axis in severe asthma. JCI Insight 2021, 6: e149945. PMID: 34591794, PMCID: PMC8663569, DOI: 10.1172/jci.insight.149945.Peer-Reviewed Original ResearchConceptsLung functionIL-18NF-κBTranscriptional hallmarksExacerbation-prone asthmaSevere asthma pathogenesisSubgroup of patientsVariable natural historySevere Asthma Research Program (SARP) cohortDownstream NF-κBMixed inflammatory processActivator protein-1 (AP-1) activationPathobiological underpinningsCorticosteroid exposureSevere asthmaAsthma clustersAsthma pathogenesisPatient morbidityInflammatory processProtein-1 activationExternal cohortLung tissuePatient clustersAP-1 activityNatural history
2014
An airway epithelial iNOS–DUOX2–thyroid peroxidase metabolome drives Th1/Th2 nitrative stress in human severe asthma
Voraphani N, Gladwin MT, Contreras AU, Kaminski N, Tedrow JR, Milosevic J, Bleecker ER, Meyers DA, Ray A, Ray P, Erzurum SC, Busse WW, Zhao J, Trudeau JB, Wenzel SE. An airway epithelial iNOS–DUOX2–thyroid peroxidase metabolome drives Th1/Th2 nitrative stress in human severe asthma. Mucosal Immunology 2014, 7: 1175-1185. PMID: 24518246, PMCID: PMC4130801, DOI: 10.1038/mi.2014.6.Peer-Reviewed Original ResearchConceptsInducible nitric oxide synthaseHuman airway epithelial cellsDual oxidase 2Severe asthmaNitrative stressThyroid peroxidaseIL-13Ex vivoSevere refractory asthmaNitric oxide synthaseTh2 cytokine expressionAirway epithelial cellsRefractory asthmaLower interleukinHigher interferonCytokine expressionOxide synthaseOxidase 2AsthmaIFNEpithelial cellsEpithelial cell systemSuperoxide dismutaseRNA knockdownEndogenous peroxidase