PMID- 36901724 OWN - NLM STAT- MEDLINE DCOM- 20230316 LR - 20231215 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 5 DP - 2023 Feb 21 TI - Electronic Cigarette Exposure Increases the Severity of Influenza a Virus Infection via TRAIL Dysregulation in Human Precision-Cut Lung Slices. LID - 10.3390/ijms24054295 [doi] LID - 4295 AB - The use of electronic nicotine dispensing systems (ENDS), also known as electronic cigarettes (ECs), is common among adolescents and young adults with limited knowledge about the detrimental effects on lung health such as respiratory viral infections and underlying mechanisms. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a protein of the TNF family involved in cell apoptosis, is upregulated in COPD patients and during influenza A virus (IAV) infections, but its role in viral infection during EC exposures remains unclear. This study was aimed to investigate the effect of ECs on viral infection and TRAIL release in a human lung precision-cut lung slices (PCLS) model, and the role of TRAIL in regulating IAV infection. PCLS prepared from lungs of nonsmoker healthy human donors were exposed to EC juice (E-juice) and IAV for up to 3 days during which viral load, TRAIL, lactate dehydrogenase (LDH), and TNF-alpha in the tissue and supernatants were determined. TRAIL neutralizing antibody and recombinant TRAIL were utilized to determine the contribution of TRAIL to viral infection during EC exposures. E-juice increased viral load, TRAIL, TNF-alpha release and cytotoxicity in IAV-infected PCLS. TRAIL neutralizing antibody increased tissue viral load but reduced viral release into supernatants. Conversely, recombinant TRAIL decreased tissue viral load but increased viral release into supernatants. Further, recombinant TRAIL enhanced the expression of interferon-beta and interferon-lambda induced by E-juice exposure in IAV-infected PCLS. Our results suggest that EC exposure in human distal lungs amplifies viral infection and TRAIL release, and that TRAIL may serve as a mechanism to regulate viral infection. Appropriate levels of TRAIL may be important to control IAV infection in EC users. FAU - Agraval, Hina AU - Agraval H AD - Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA. FAU - Crue, Taylor AU - Crue T AUID- ORCID: 0000-0002-8469-9546 AD - School of Medicine, University of Colorado, 12700 E 19th Ave, Aurora, CO 80045, USA. FAU - Schaunaman, Niccolette AU - Schaunaman N AD - Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA. FAU - Numata, Mari AU - Numata M AD - Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA. FAU - Day, Brian J AU - Day BJ AD - Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA. FAU - Chu, Hong Wei AU - Chu HW AD - Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA. LA - eng GR - R01 HL144396/HL/NHLBI NIH HHS/United States GR - R01 HL144396/NH/NIH HHS/United States PT - Journal Article DEP - 20230221 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antibodies, Neutralizing) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (TNFSF10 protein, human) SB - IM MH - Adolescent MH - Humans MH - Young Adult MH - Antibodies, Neutralizing/metabolism MH - *Electronic Nicotine Delivery Systems MH - *Influenza A virus/physiology MH - *Influenza, Human MH - Lung/pathology MH - Tumor Necrosis Factor-alpha/metabolism PMC - PMC10002047 OTO - NOTNLM OT - Influenza A virus OT - PCLS OT - TRAIL OT - electronic cigarettes COIS- The authors declare no conflict of interest. EDAT- 2023/03/12 06:00 MHDA- 2023/03/15 06:00 PMCR- 2023/02/21 CRDT- 2023/03/11 01:15 PHST- 2023/01/25 00:00 [received] PHST- 2023/02/09 00:00 [revised] PHST- 2023/02/19 00:00 [accepted] PHST- 2023/03/11 01:15 [entrez] PHST- 2023/03/12 06:00 [pubmed] PHST- 2023/03/15 06:00 [medline] PHST- 2023/02/21 00:00 [pmc-release] AID - ijms24054295 [pii] AID - ijms-24-04295 [pii] AID - 10.3390/ijms24054295 [doi] PST - epublish SO - Int J Mol Sci. 2023 Feb 21;24(5):4295. doi: 10.3390/ijms24054295.