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Lung Inflammation Induced by Inactivated SARS-CoV-2 in C57BL/6 Female Mice Is Controlled by Intranasal Instillation of Vitamin D
The COVID-19 pandemic was triggered by the coronavirus SARS-CoV-2, whose peak occurred in the years 2020 and 2021. The main target of this virus is the lung, and the infection is associated with an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we descri...
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Published in: | Cells (Basel, Switzerland) Switzerland), 2023-04, Vol.12 (7), p.1092 |
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creator | Fernandes de Souza, William Danilo Zorzella-Pezavento, Sofia Fernanda Gonçalves Ayupe, Marina Caçador Salgado, Caio Loureiro Oliveira, Bernardo de Castro Moreira, Francielly da Silva, Guilherme William Muraro, Stefanie Primon de Souza, Gabriela Fabiano Proença-Módena, José Luiz Araujo Junior, Joao Pessoa Fonseca, Denise Morais da Sartori, Alexandrina |
description | The COVID-19 pandemic was triggered by the coronavirus SARS-CoV-2, whose peak occurred in the years 2020 and 2021. The main target of this virus is the lung, and the infection is associated with an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 female mice, and then the evaluation of the ability of vitamin D (VitD) to control this process. The assays used to estimate the severity of lung involvement included the total and differential number of cells in the bronchoalveolar lavage fluid (BALF), histopathological analysis, quantification of T cell subsets, and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates, and flow cytometric analysis of cells recovered from lung parenchyma. The IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in transgenic mice infected with SARS-CoV-2. This inflammatory process was significantly decreased by the IN delivery of VitD, but not by its IP administration, suggesting that this hormone could have a therapeutic potential in COVID-19 if locally applied. To our knowledge, the local delivery of VitD to downmodulate lung inflammation in COVID-19 is an original proposition. |
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The main target of this virus is the lung, and the infection is associated with an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 female mice, and then the evaluation of the ability of vitamin D (VitD) to control this process. The assays used to estimate the severity of lung involvement included the total and differential number of cells in the bronchoalveolar lavage fluid (BALF), histopathological analysis, quantification of T cell subsets, and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates, and flow cytometric analysis of cells recovered from lung parenchyma. The IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in transgenic mice infected with SARS-CoV-2. This inflammatory process was significantly decreased by the IN delivery of VitD, but not by its IP administration, suggesting that this hormone could have a therapeutic potential in COVID-19 if locally applied. To our knowledge, the local delivery of VitD to downmodulate lung inflammation in COVID-19 is an original proposition.</description><identifier>ISSN: 2073-4409</identifier><identifier>EISSN: 2073-4409</identifier><identifier>DOI: 10.3390/cells12071092</identifier><identifier>PMID: 37048165</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Alfacalcidol ; Animals ; Asymptomatic ; Bacterial pneumonia ; Bronchus ; Calcifediol ; Care and treatment ; Coronaviruses ; COVID-19 ; Cytokine storm ; Diagnosis ; Dosage and administration ; Drug delivery systems ; Drug dosages ; Drugs ; Female ; Flow cytometry ; Humans ; Immune system ; Infections ; Inflammation ; Intranasal medication ; Investigations ; Lavage ; lung ; Lungs ; Lymphocytes T ; Methods ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nervous system ; Neutrophils ; Pandemics ; Parenchyma ; Pathogens ; Pneumonia ; SARS-CoV-2 ; Severe acute respiratory syndrome coronavirus 2 ; Transgenic mice ; Vehicles ; Viral infections ; Vitamin D ; Vitamin D - pharmacology ; Vitamins</subject><ispartof>Cells (Basel, Switzerland), 2023-04, Vol.12 (7), p.1092</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c505t-e05e8770c7f1157729ee6c122ea7465f96881c81e72bd4ba2e6d9651e43a469b3</cites><orcidid>0000-0002-3398-6035 ; 0000-0002-9153-1485 ; 0000-0002-4996-3153 ; 0000-0001-9610-694X ; 0000-0002-5105-6659</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2799601563?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2799601563?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,38516,43895,44590,53791,53793,74412,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37048165$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fernandes de Souza, William Danilo</creatorcontrib><creatorcontrib>Zorzella-Pezavento, Sofia Fernanda Gonçalves</creatorcontrib><creatorcontrib>Ayupe, Marina Caçador</creatorcontrib><creatorcontrib>Salgado, Caio Loureiro</creatorcontrib><creatorcontrib>Oliveira, Bernardo de Castro</creatorcontrib><creatorcontrib>Moreira, Francielly</creatorcontrib><creatorcontrib>da Silva, Guilherme William</creatorcontrib><creatorcontrib>Muraro, Stefanie Primon</creatorcontrib><creatorcontrib>de Souza, Gabriela Fabiano</creatorcontrib><creatorcontrib>Proença-Módena, José Luiz</creatorcontrib><creatorcontrib>Araujo Junior, Joao Pessoa</creatorcontrib><creatorcontrib>Fonseca, Denise Morais da</creatorcontrib><creatorcontrib>Sartori, Alexandrina</creatorcontrib><title>Lung Inflammation Induced by Inactivated SARS-CoV-2 in C57BL/6 Female Mice Is Controlled by Intranasal Instillation of Vitamin D</title><title>Cells (Basel, Switzerland)</title><addtitle>Cells</addtitle><description>The COVID-19 pandemic was triggered by the coronavirus SARS-CoV-2, whose peak occurred in the years 2020 and 2021. The main target of this virus is the lung, and the infection is associated with an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 female mice, and then the evaluation of the ability of vitamin D (VitD) to control this process. The assays used to estimate the severity of lung involvement included the total and differential number of cells in the bronchoalveolar lavage fluid (BALF), histopathological analysis, quantification of T cell subsets, and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates, and flow cytometric analysis of cells recovered from lung parenchyma. The IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in transgenic mice infected with SARS-CoV-2. This inflammatory process was significantly decreased by the IN delivery of VitD, but not by its IP administration, suggesting that this hormone could have a therapeutic potential in COVID-19 if locally applied. To our knowledge, the local delivery of VitD to downmodulate lung inflammation in COVID-19 is an original proposition.</description><subject>Alfacalcidol</subject><subject>Animals</subject><subject>Asymptomatic</subject><subject>Bacterial pneumonia</subject><subject>Bronchus</subject><subject>Calcifediol</subject><subject>Care and treatment</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Cytokine storm</subject><subject>Diagnosis</subject><subject>Dosage and administration</subject><subject>Drug delivery systems</subject><subject>Drug dosages</subject><subject>Drugs</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Humans</subject><subject>Immune system</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Intranasal medication</subject><subject>Investigations</subject><subject>Lavage</subject><subject>lung</subject><subject>Lungs</subject><subject>Lymphocytes T</subject><subject>Methods</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Nervous system</subject><subject>Neutrophils</subject><subject>Pandemics</subject><subject>Parenchyma</subject><subject>Pathogens</subject><subject>Pneumonia</subject><subject>SARS-CoV-2</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Transgenic mice</subject><subject>Vehicles</subject><subject>Viral infections</subject><subject>Vitamin D</subject><subject>Vitamin D - 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The IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in transgenic mice infected with SARS-CoV-2. This inflammatory process was significantly decreased by the IN delivery of VitD, but not by its IP administration, suggesting that this hormone could have a therapeutic potential in COVID-19 if locally applied. To our knowledge, the local delivery of VitD to downmodulate lung inflammation in COVID-19 is an original proposition.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>37048165</pmid><doi>10.3390/cells12071092</doi><orcidid>https://orcid.org/0000-0002-3398-6035</orcidid><orcidid>https://orcid.org/0000-0002-9153-1485</orcidid><orcidid>https://orcid.org/0000-0002-4996-3153</orcidid><orcidid>https://orcid.org/0000-0001-9610-694X</orcidid><orcidid>https://orcid.org/0000-0002-5105-6659</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Alfacalcidol Animals Asymptomatic Bacterial pneumonia Bronchus Calcifediol Care and treatment Coronaviruses COVID-19 Cytokine storm Diagnosis Dosage and administration Drug delivery systems Drug dosages Drugs Female Flow cytometry Humans Immune system Infections Inflammation Intranasal medication Investigations Lavage lung Lungs Lymphocytes T Methods Mice Mice, Inbred C57BL Mice, Transgenic Nervous system Neutrophils Pandemics Parenchyma Pathogens Pneumonia SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Transgenic mice Vehicles Viral infections Vitamin D Vitamin D - pharmacology Vitamins |
title | Lung Inflammation Induced by Inactivated SARS-CoV-2 in C57BL/6 Female Mice Is Controlled by Intranasal Instillation of Vitamin D |
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