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Viral stimulation modulates endotype-related ACE2 expression in eosinophilic chronic rhinosinusitis.
Rhinology. 2021 Jul 20 [Online ahead of print]R

Abstract

BACKGROUND

Angiotensin-converting enzyme 2 (ACE2), a receptor targeted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the nasal mucosa. Chronic rhinosinusitis (CRS) shows diverse endotypes and is aggravated by viral infection. Whether viral stimulation and CRS endotype influence ACE2 expression remains unclear. We investigated the expression of ACE2 and the transmembrane protease, serine 2 (TMPRSS2), which mediate the entry of SARS-CoV-2 into cells, and assessed polyinosinic:polycytidylic acid (poly[I:C])-induced changes based on CRS endotype.

METHODOLOGY

ACE2 and TMPRSS2 expression was evaluated based on CRS phenotype, endotype, and tissue type. Correlations between ACE2/TMPRSS2 expression and inflammatory mediators in nasal polyps (NP) were examined. Air-liquid interface culture experiments were performed to assess the effects of major cytokines or poly(I:C) stimulation on ACE2/TMPRSS2 expression in primary epithelial cells from healthy nasal mucosa, eosinophilic NP (ENP), and non-eosinophilic NP (NENP).

RESULTS

In primary nasal epithelial cells, interleukin (IL)-13 decreased ACE2 expression but increased TMPRSS2. Eosinophilic CRS showed lower ACE2 expression than non-eosinophilic CRS, regardless of CRS phenotype. CRS endotype was an independent factor associated with ACE2/TMPRSS2 expression in NP. Serum and tissue eosinophilic marker levels were inversely correlated with ACE2 expression, whereas tissue neutrophilic marker levels and ACE2 expression were positively correlated in NP. ACE2 expression was suppressed in ENP tissues; however, a combination of poly(I:C) and IL-13 induced ACE2/TMPRSS2 upregulation in ENP.

CONCLUSIONS

ENP tissues have lower ACE2 expression than NENP; however, viral stimulation promotes ACE2/TMPRSS2 upregulation in ENP.

Authors+Show Affiliations

Department of Otorhinolaryngology, Seoul National University College of Medicine, Boramae Medical Center, Seoul, Republic of Korea. Sensory Organ Research Institute, Seoul National University Medical Research Center.Department of Otorhinolaryngology, Seoul National University College of Medicine, Boramae Medical Center, Seoul, Republic of Korea. Sensory Organ Research Institute, Seoul National University Medical Research Center.Department of Otorhinolaryngology, Seoul National University College of Medicine, Boramae Medical Center, Seoul, Republic of Korea. Sensory Organ Research Institute, Seoul National University Medical Research Center.Department of Otorhinolaryngology, Seoul National University College of Medicine, Boramae Medical Center, Seoul, Republic of Korea. Sensory Organ Research Institute, Seoul National University Medical Research Center.Department of Otorhinolaryngology, Seoul National University College of Medicine, Boramae Medical Center, Seoul, Republic of Korea. Sensory Organ Research Institute, Seoul National University Medical Research Center.Department of Otorhinolaryngology, Seoul National University College of Medicine, Boramae Medical Center, Seoul, Republic of Korea. Sensory Organ Research Institute, Seoul National University Medical Research Center.Department of Otorhinolaryngology, Seoul National University College of Medicine, Boramae Medical Center, Seoul, Republic of Korea. Sensory Organ Research Institute, Seoul National University Medical Research Center.Department of Otorhinolaryngology, Seoul National University College of Medicine, Boramae Medical Center, Seoul, Republic of Korea. Sensory Organ Research Institute, Seoul National University Medical Research Center.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34282808

Citation

Hong, S-N, et al. "Viral Stimulation Modulates Endotype-related ACE2 Expression in Eosinophilic Chronic Rhinosinusitis." Rhinology, 2021.
Hong SN, Kim JK, Kim JA, et al. Viral stimulation modulates endotype-related ACE2 expression in eosinophilic chronic rhinosinusitis. Rhinology. 2021.
Hong, S. N., Kim, J. K., Kim, J. A., Cha, H., Kim, J. Y., Lim, H. S., Eun, K. M., & Kim, D. W. (2021). Viral stimulation modulates endotype-related ACE2 expression in eosinophilic chronic rhinosinusitis. Rhinology. https://doi.org/10.4193/Rhin21.001
Hong SN, et al. Viral Stimulation Modulates Endotype-related ACE2 Expression in Eosinophilic Chronic Rhinosinusitis. Rhinology. 2021 Jul 20; PubMed PMID: 34282808.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Viral stimulation modulates endotype-related ACE2 expression in eosinophilic chronic rhinosinusitis. AU - Hong,S-N, AU - Kim,J K, AU - Kim,J-A, AU - Cha,H, AU - Kim,J Y, AU - Lim,H-S, AU - Eun,K M, AU - Kim,D W, Y1 - 2021/07/20/ PY - 2021/7/20/entrez PY - 2021/7/21/pubmed PY - 2021/7/21/medline JF - Rhinology JO - Rhinology N2 - BACKGROUND: Angiotensin-converting enzyme 2 (ACE2), a receptor targeted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the nasal mucosa. Chronic rhinosinusitis (CRS) shows diverse endotypes and is aggravated by viral infection. Whether viral stimulation and CRS endotype influence ACE2 expression remains unclear. We investigated the expression of ACE2 and the transmembrane protease, serine 2 (TMPRSS2), which mediate the entry of SARS-CoV-2 into cells, and assessed polyinosinic:polycytidylic acid (poly[I:C])-induced changes based on CRS endotype. METHODOLOGY: ACE2 and TMPRSS2 expression was evaluated based on CRS phenotype, endotype, and tissue type. Correlations between ACE2/TMPRSS2 expression and inflammatory mediators in nasal polyps (NP) were examined. Air-liquid interface culture experiments were performed to assess the effects of major cytokines or poly(I:C) stimulation on ACE2/TMPRSS2 expression in primary epithelial cells from healthy nasal mucosa, eosinophilic NP (ENP), and non-eosinophilic NP (NENP). RESULTS: In primary nasal epithelial cells, interleukin (IL)-13 decreased ACE2 expression but increased TMPRSS2. Eosinophilic CRS showed lower ACE2 expression than non-eosinophilic CRS, regardless of CRS phenotype. CRS endotype was an independent factor associated with ACE2/TMPRSS2 expression in NP. Serum and tissue eosinophilic marker levels were inversely correlated with ACE2 expression, whereas tissue neutrophilic marker levels and ACE2 expression were positively correlated in NP. ACE2 expression was suppressed in ENP tissues; however, a combination of poly(I:C) and IL-13 induced ACE2/TMPRSS2 upregulation in ENP. CONCLUSIONS: ENP tissues have lower ACE2 expression than NENP; however, viral stimulation promotes ACE2/TMPRSS2 upregulation in ENP. SN - 0300-0729 UR - https://www.unboundmedicine.com/medline/citation/34282808/Viral_stimulation_modulates_endotype-related_ACE2_expression_in_eosinophilic_chronic_rhinosinusitis. L2 - https://www.rhinologyjournal.com/Abstract.php?id=2910 DB - PRIME DP - Unbound Medicine ER -
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