In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection

Ayman Mubarak,1 Bahauddeen Alrfaei,2 Abdullah Aljurayyan,3 Mahfoudh M Alqafil,1 Mohamed A Farrag,1 Maaweya E Hamed,1 Bandar Alosaimi,4 Fahad Almajhdi,1 Wael Alturaiki5 1Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia; 2Stem Cells Unit, Department...

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Autores principales:	Mubarak A, Alrfaei B, Aljurayyan A, Alqafil MM, Farrag MA, Hamed ME, Alosaimi B, Almajhdi F, Alturaiki W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	mers-cov proinflammatory cytokines regulatory cytokines anti-dpp4 ifns a549 lung cells Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/98dc12aec7514c14b87a079d165c2dda
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spelling	oai:doaj.org-article:98dc12aec7514c14b87a079d165c2dda2021-12-02T15:44:38ZIn vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection1178-7031https://doaj.org/article/98dc12aec7514c14b87a079d165c2dda2021-05-01T00:00:00Zhttps://www.dovepress.com/in-vivo-and-in-vitro-evaluation-of-cytokine-expression-profiles-during-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Ayman Mubarak,1 Bahauddeen Alrfaei,2 Abdullah Aljurayyan,3 Mahfoudh M Alqafil,1 Mohamed A Farrag,1 Maaweya E Hamed,1 Bandar Alosaimi,4 Fahad Almajhdi,1 Wael Alturaiki5 1Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia; 2Stem Cells Unit, Department of Cellular Therapy, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Science, MNGHA, Riyadh, Saudi Arabia; 3Immunology and HLA Department, Pathology and Laboratory Medicine, King Fahad Medical City, Riyadh, Saudi Arabia; 4Research Center, King Fahad Medical City, Riyadh, Saudi Arabia; 5Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi ArabiaCorrespondence: Wael AlturaikiDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi ArabiaEmail w.alturaiki@mu.edu.saBackground: Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in the Kingdom of Saudi Arabia, is associated with a high mortality rate.Aim: To determine the effect of MERS-CoV on the immune response in infected patients and investigate cytokine production in the A549 epithelial cell line in response to a recombinant MERS-CoV spike protein (rSP) in the presence or absence of anti-dipeptidyl peptidase 4 (DPP4) antibody (3 independent experiments). Cytokine levels were measured using a cytokine ELISA array.Methods: A Bio-Plex multiplex assay and cytokine ELISA were used in our study to measure the cytokine levels.Results: Comparative analysis of MERS-CoV-infected patients (4 samples) and noninfected healthy controls (HCs) (5 samples) showed that serum levels of the following cytokines and chemokines were significantly higher in MERS-CoV patients than in the HCs (*p < 0.05): interferon (IFN)-α 2 (43.4 vs 5.4), IFN-β (17.7 vs 6.2), IFN-γ (43.4 vs 9.7), interleukin (IL)-8 (13.7 vs 0), IL-2 (11.2 vs 3), IL-27p28 (57.8 vs 13.8), and IL-35 (167.5 vs 87.5).Discussion: Our results revealed that MERS-CoV infection induced a slight increase in IFN levels but triggered a more pronounced increase in expression of the regulatory cytokines IL-27 and IL-35. A recombinant version of the full-length MERS-CoV spike protein increased the expression of IL-8 (160 pg/mL), IL-2 (100 pg/mL) and IL-12 (65 pg/mL) in A549 lung epithelial cells compared to that in the unstimulated control cells. The presence of anti-DPP4 antibody did not affect cytokine suppression or induction in A549 cells in vitro but decreased the level of IL-8 from 160 pg/mL to 65 pg/mL.Conclusion: MERS-CoV can decrease IFN levels to interfere with the IFN pathway and enhance the production of regulatory cytokines. Inhibition of the increases in IL-27 and IL-35 may contribute to halting MERS-CoV in the early stage of infection.Keywords: MERS-CoV, proinflammatory cytokines, regulatory cytokines, anti-DPP4, IFNs, A549 lung cellsMubarak AAlrfaei BAljurayyan AAlqafil MMFarrag MAHamed MEAlosaimi BAlmajhdi FAlturaiki WDove Medical Pressarticlemers-covproinflammatory cytokinesregulatory cytokinesanti-dpp4ifnsa549 lung cellsPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 2121-2131 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mers-cov proinflammatory cytokines regulatory cytokines anti-dpp4 ifns a549 lung cells Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	mers-cov proinflammatory cytokines regulatory cytokines anti-dpp4 ifns a549 lung cells Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Mubarak A Alrfaei B Aljurayyan A Alqafil MM Farrag MA Hamed ME Alosaimi B Almajhdi F Alturaiki W In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection
description	Ayman Mubarak,1 Bahauddeen Alrfaei,2 Abdullah Aljurayyan,3 Mahfoudh M Alqafil,1 Mohamed A Farrag,1 Maaweya E Hamed,1 Bandar Alosaimi,4 Fahad Almajhdi,1 Wael Alturaiki5 1Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia; 2Stem Cells Unit, Department of Cellular Therapy, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Science, MNGHA, Riyadh, Saudi Arabia; 3Immunology and HLA Department, Pathology and Laboratory Medicine, King Fahad Medical City, Riyadh, Saudi Arabia; 4Research Center, King Fahad Medical City, Riyadh, Saudi Arabia; 5Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi ArabiaCorrespondence: Wael AlturaikiDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi ArabiaEmail w.alturaiki@mu.edu.saBackground: Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in the Kingdom of Saudi Arabia, is associated with a high mortality rate.Aim: To determine the effect of MERS-CoV on the immune response in infected patients and investigate cytokine production in the A549 epithelial cell line in response to a recombinant MERS-CoV spike protein (rSP) in the presence or absence of anti-dipeptidyl peptidase 4 (DPP4) antibody (3 independent experiments). Cytokine levels were measured using a cytokine ELISA array.Methods: A Bio-Plex multiplex assay and cytokine ELISA were used in our study to measure the cytokine levels.Results: Comparative analysis of MERS-CoV-infected patients (4 samples) and noninfected healthy controls (HCs) (5 samples) showed that serum levels of the following cytokines and chemokines were significantly higher in MERS-CoV patients than in the HCs (*p < 0.05): interferon (IFN)-α 2 (43.4 vs 5.4), IFN-β (17.7 vs 6.2), IFN-γ (43.4 vs 9.7), interleukin (IL)-8 (13.7 vs 0), IL-2 (11.2 vs 3), IL-27p28 (57.8 vs 13.8), and IL-35 (167.5 vs 87.5).Discussion: Our results revealed that MERS-CoV infection induced a slight increase in IFN levels but triggered a more pronounced increase in expression of the regulatory cytokines IL-27 and IL-35. A recombinant version of the full-length MERS-CoV spike protein increased the expression of IL-8 (160 pg/mL), IL-2 (100 pg/mL) and IL-12 (65 pg/mL) in A549 lung epithelial cells compared to that in the unstimulated control cells. The presence of anti-DPP4 antibody did not affect cytokine suppression or induction in A549 cells in vitro but decreased the level of IL-8 from 160 pg/mL to 65 pg/mL.Conclusion: MERS-CoV can decrease IFN levels to interfere with the IFN pathway and enhance the production of regulatory cytokines. Inhibition of the increases in IL-27 and IL-35 may contribute to halting MERS-CoV in the early stage of infection.Keywords: MERS-CoV, proinflammatory cytokines, regulatory cytokines, anti-DPP4, IFNs, A549 lung cells
format	article
author	Mubarak A Alrfaei B Aljurayyan A Alqafil MM Farrag MA Hamed ME Alosaimi B Almajhdi F Alturaiki W
author_facet	Mubarak A Alrfaei B Aljurayyan A Alqafil MM Farrag MA Hamed ME Alosaimi B Almajhdi F Alturaiki W
author_sort	Mubarak A
title	In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection
title_short	In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection
title_full	In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection
title_fullStr	In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection
title_full_unstemmed	In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection
title_sort	in vivo and in vitro evaluation of cytokine expression profiles during middle east respiratory syndrome coronavirus (mers-cov) infection
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/98dc12aec7514c14b87a079d165c2dda
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In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection

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