PMID- 34314863 OWN - NLM STAT- MEDLINE DCOM- 20210915 LR - 20221221 IS - 1873-1597 (Electronic) IS - 1572-1000 (Print) IS - 1572-1000 (Linking) VI - 35 DP - 2021 Sep TI - Ultraviolet-A light reduces cellular cytokine release from human endotracheal cells infected with Coronavirus. PG - 102457 LID - S1572-1000(21)00281-7 [pii] LID - 10.1016/j.pdpdt.2021.102457 [doi] AB - BACKGROUND: An important clinical feature of coronavirus disease 2019 (COVID-19) is hypercytokinemia (cytokine storm). We previously showed that narrow band ultraviolet-A (NB-UVA) treatment salvages coronavirus (CoV)-229E-infected human tracheal cells, and that daily endotracheal NB-UVA therapy reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels in human subjects, with improved clinical outcomes. Here, we examined NB-UVA effects on cytokine release during CoV-229E infection. METHODS: Primary human tracheal epithelial cells were transfected with CoV-229E, then exposed to 2 mW/cm(2) NB-UVA for 20 minutes every 24h, either 3 or 4 times. Secreted cytokine/chemokine levels were analyzed in supernatants collected from CoV-229E-infected/UVA-exposed cells 24h after the last UVA treatment, and from matched non-infected/UVA-exposed controls, CoV-229E-infected/non-exposed controls, and non-infected/non-exposed (naive) controls. Metabolic pathway/downstream prediction analyses were also performed. RESULTS: Pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF), and chemokines IL-8, monocyte chemoattractant protein-1 (MCP1), and interferon gamma-induced protein 10 (IP-10), were significantly increased in CoV-229E-infected cells, and significantly decreased following NB-UVA treatment. Interferon (IFN)-alpha2, IFN-gamma, and IL-10 were not upregulated in response to CoV-229E. Metabolic pathway predictions indicated hypercytokinemia as the top inflammatory response in CoV-229E-infected cells, whereas the top predicted pathway in CoV-229E-infected/UVA-exposed cells was the recovery stage of severe acute respiratory syndrome. CONCLUSIONS: Human tracheal epithelial cells infected with CoV-229E showed reduced cytokine secretions including IL-6, TNF, IL-8, and MCP-1, following NB-UVA exposure. This reduction of cytokine levels in vitro, coupled with previously identified reduced cell death in CoV-229E-infected/UVA-exposed cells, suggests that determining UVA effects on cytokine storm in human SARS-Co-V2 patients is warranted. CI - Copyright (c) 2021. Published by Elsevier B.V. FAU - Leite, Gabriela AU - Leite G AD - Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA. FAU - Pimentel, Mark AU - Pimentel M AD - Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA; Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai, Los Angeles, CA, USA. FAU - Mathur, Ruchi AU - Mathur R AD - Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai, Los Angeles, CA, USA. FAU - Barlow, Gillian M AU - Barlow GM AD - Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA. FAU - Chan, Yin AU - Chan Y AD - Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai, Los Angeles, CA, USA. FAU - Melmed, Gil Y AU - Melmed GY AD - Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai, Los Angeles, CA, USA. FAU - Rezaie, Ali AU - Rezaie A AD - Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA; Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai, Los Angeles, CA, USA. Electronic address: ali.rezaie@cshs.org. LA - eng PT - Journal Article DEP - 20210724 PL - Netherlands TA - Photodiagnosis Photodyn Ther JT - Photodiagnosis and photodynamic therapy JID - 101226123 RN - 0 (Cytokines) RN - 0 (Photosensitizing Agents) SB - IM MH - *COVID-19 MH - Cytokines MH - Humans MH - *Photochemotherapy/methods MH - Photosensitizing Agents MH - SARS-CoV-2 PMC - PMC8310417 OTO - NOTNLM OT - COVID-19 OT - Coronavirus-229E OT - Cytokine storm OT - Human tracheal epithelial cells OT - Interleukin-6 OT - Tumor necrosis factor OT - UV-A OT - Ultraviolet light-A COIS- Cedars-Sinai has a patent on internal UV therapy, inventors: AR, MP, GM, RM and GL. The rest of the authors declare no other financial conflicts of interest. Cedars-Sinai has a licensing agreement with Aytu BioSciences. EDAT- 2021/07/28 06:00 MHDA- 2021/09/16 06:00 PMCR- 2021/07/24 CRDT- 2021/07/27 20:17 PHST- 2021/06/16 00:00 [received] PHST- 2021/07/12 00:00 [revised] PHST- 2021/07/22 00:00 [accepted] PHST- 2021/07/28 06:00 [pubmed] PHST- 2021/09/16 06:00 [medline] PHST- 2021/07/27 20:17 [entrez] PHST- 2021/07/24 00:00 [pmc-release] AID - S1572-1000(21)00281-7 [pii] AID - 102457 [pii] AID - 10.1016/j.pdpdt.2021.102457 [doi] PST - ppublish SO - Photodiagnosis Photodyn Ther. 2021 Sep;35:102457. doi: 10.1016/j.pdpdt.2021.102457. Epub 2021 Jul 24.