Ultraviolet-A light reduces cellular cytokine release from human endotracheal cells infected with Coronavirus

Gabriela Leite; Mark Pimentel; Ruchi Mathur; Gillian M Barlow; Yin Chan; Gil Y Melmed; Ali Rezaie

doi:10.1016/j.pdpdt.2021.102457

Ultraviolet-A light reduces cellular cytokine release from human endotracheal cells infected with Coronavirus

Photodiagnosis Photodyn Ther. 2021 Sep:35:102457. doi: 10.1016/j.pdpdt.2021.102457. Epub 2021 Jul 24.

Authors

Gabriela Leite¹, Mark Pimentel², Ruchi Mathur³, Gillian M Barlow¹, Yin Chan⁴, Gil Y Melmed⁴, Ali Rezaie⁵

Affiliations

¹ Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA.
² 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.
³ 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.
⁴ Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai, Los Angeles, CA, USA.
⁵ 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.

Abstract

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/cm² 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 (naïve) 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)-α2, IFN-γ, 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.

Keywords: COVID-19; Coronavirus-229E; Cytokine storm; Human tracheal epithelial cells; Interleukin-6; Tumor necrosis factor; UV-A; Ultraviolet light-A.

MeSH terms

COVID-19*
Cytokines
Humans
Photochemotherapy* / methods
Photosensitizing Agents
SARS-CoV-2

Substances

Cytokines
Photosensitizing Agents