Chronic alcohol use primes bronchial cells for altered inflammatory response and barrier dysfunction during SARS-CoV-2 infection
Alcohol use disorder (AUD) is a significant public health concern and people with AUD are more likely to develop severe acute respiratory distress syndrome (ARDS) in response to respiratory infections. To examine whether AUD was a risk factor for more severe outcome in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we examined early responses to infection using cultured differentiated bronchial epithelial cells derived from brushings obtained from people with AUD or without AUD. RNA-seq analysis of uninfected cells determined that AUD cells were enriched for expression of epidermal genes as compared with non-AUD cells. Bronchial epithelial cells from patients with AUD showed a significant decrease in barrier function 72 h postinfection, as determined by transepithelial electrical resistance. In contrast, barrier function of non-AUD cells was enhanced 72 h after SARS-CoV-2 infection. AUD cells showed claudin-7 that did not colocalize with zonula occludens-1 (ZO-1), indicative of disorganized tight junctions. However, both AUD and non-AUD cells showed decreased β-catenin expression following SARS-CoV-2 infection. To determine the impact of AUD on the inflammatory response to SARS-CoV-2 infection, cytokine secretion was measured by multiplex analysis. SARS-CoV-2-infected AUD bronchial cells had enhanced secretion of multiple proinflammatory cytokines including TNFα, IL-1β, and IFNγ as opposed to non-AUD cells. In contrast, secretion of the barrier-protective cytokines epidermal growth factor (EGF) and granulocyte macrophage-colony stimulating factor (GM-CSF) was enhanced for non-AUD bronchial cells. Taken together, these data support the hypothesis that AUD is a risk factor for COVID-19, where alcohol primes airway epithelial cells for increased inflammation and increased barrier dysfunction and increased inflammation in response to infection by SARS-CoV-2.NEW & NOTEWORTHY Alcohol use disorder (AUD) is a significant risk factor for severe acute respiratory distress syndrome. We found that AUD causes a phenotypic shift in gene expression in human bronchial epithelial cells, enhancing expression of epidermal genes. AUD cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had higher levels of proinflammatory cytokine secretion and barrier dysfunction not present in infected non-AUD cells, consistent with increased early COVID-19 severity due to AUD.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:325 |
|---|---|
| Enthalten in: |
American journal of physiology. Lung cellular and molecular physiology - 325(2023), 5 vom: 01. Nov., Seite L647-L661 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Easley, Kristen F [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 06.11.2023 Date Revised 09.11.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1152/ajplung.00381.2022 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM362807531 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM362807531 | ||
| 003 | DE-627 | ||
| 005 | 20231226092018.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1152/ajplung.00381.2022 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1209.xml |
| 035 | |a (DE-627)NLM362807531 | ||
| 035 | |a (NLM)37786945 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Easley, Kristen F |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Chronic alcohol use primes bronchial cells for altered inflammatory response and barrier dysfunction during SARS-CoV-2 infection |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 06.11.2023 | ||
| 500 | |a Date Revised 09.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Alcohol use disorder (AUD) is a significant public health concern and people with AUD are more likely to develop severe acute respiratory distress syndrome (ARDS) in response to respiratory infections. To examine whether AUD was a risk factor for more severe outcome in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we examined early responses to infection using cultured differentiated bronchial epithelial cells derived from brushings obtained from people with AUD or without AUD. RNA-seq analysis of uninfected cells determined that AUD cells were enriched for expression of epidermal genes as compared with non-AUD cells. Bronchial epithelial cells from patients with AUD showed a significant decrease in barrier function 72 h postinfection, as determined by transepithelial electrical resistance. In contrast, barrier function of non-AUD cells was enhanced 72 h after SARS-CoV-2 infection. AUD cells showed claudin-7 that did not colocalize with zonula occludens-1 (ZO-1), indicative of disorganized tight junctions. However, both AUD and non-AUD cells showed decreased β-catenin expression following SARS-CoV-2 infection. To determine the impact of AUD on the inflammatory response to SARS-CoV-2 infection, cytokine secretion was measured by multiplex analysis. SARS-CoV-2-infected AUD bronchial cells had enhanced secretion of multiple proinflammatory cytokines including TNFα, IL-1β, and IFNγ as opposed to non-AUD cells. In contrast, secretion of the barrier-protective cytokines epidermal growth factor (EGF) and granulocyte macrophage-colony stimulating factor (GM-CSF) was enhanced for non-AUD bronchial cells. Taken together, these data support the hypothesis that AUD is a risk factor for COVID-19, where alcohol primes airway epithelial cells for increased inflammation and increased barrier dysfunction and increased inflammation in response to infection by SARS-CoV-2.NEW & NOTEWORTHY Alcohol use disorder (AUD) is a significant risk factor for severe acute respiratory distress syndrome. We found that AUD causes a phenotypic shift in gene expression in human bronchial epithelial cells, enhancing expression of epidermal genes. AUD cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had higher levels of proinflammatory cytokine secretion and barrier dysfunction not present in infected non-AUD cells, consistent with increased early COVID-19 severity due to AUD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a airway epithelia | |
| 650 | 4 | |a alcohol use disorder | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a tight junction | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 700 | 1 | |a Edenfield, R Clayton |e verfasserin |4 aut | |
| 700 | 1 | |a Lott, Megan E J |e verfasserin |4 aut | |
| 700 | 1 | |a Reed, Ryan C |e verfasserin |4 aut | |
| 700 | 1 | |a Das Sarma, Jayasri |e verfasserin |4 aut | |
| 700 | 1 | |a Mehta, Ashish J |e verfasserin |4 aut | |
| 700 | 1 | |a Staitieh, Bashar S |e verfasserin |4 aut | |
| 700 | 1 | |a Lipp, Erin K |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, In Ki |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Scott K |e verfasserin |4 aut | |
| 700 | 1 | |a Jones, Cheryl A |e verfasserin |4 aut | |
| 700 | 1 | |a Bebin-Blackwell, Anne-Gaelle |e verfasserin |4 aut | |
| 700 | 1 | |a Levy, Joshua M |e verfasserin |4 aut | |
| 700 | 1 | |a Tompkins, S Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Easley, Charles A |c 4th |e verfasserin |4 aut | |
| 700 | 1 | |a Koval, Michael |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t American journal of physiology. Lung cellular and molecular physiology |d 2000 |g 325(2023), 5 vom: 01. Nov., Seite L647-L661 |w (DE-627)NLM105748501 |x 1522-1504 |7 nnns |
| 773 | 1 | 8 | |g volume:325 |g year:2023 |g number:5 |g day:01 |g month:11 |g pages:L647-L661 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1152/ajplung.00381.2022 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 325 |j 2023 |e 5 |b 01 |c 11 |h L647-L661 | ||