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Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress

1
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-FCFRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-903, Brazil
2
Programa de Pós-Graduação em Imunologia Básica e Aplicada-PPGIBA, Instituto de Ciências Biológicas, Universidade Federal do Amazonas-UFAM, Manaus 69080-900, Brazil
3
Departamento de Biologia Básica e Oral, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo-USP, Ribeirão Preto 14040-904, Brazil
4
Departamento de Enfermagem Geral e Especializada, Escola de Enfermagem de Ribeirão Preto-EERP, Universidade de São Paulo-USP, Ribeirão Preto 14040-902, Brazil
5
Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-900, Brazil
6
Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto-FFCLRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-901, Brazil
7
Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-900, Brazil
8
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-900, Brazil
9
Hospital Santa Casa de Misericórdia de Ribeirão Preto, Ribeirão Preto 14085-000, Brazil
10
Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-900, Brazil
11
Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirão Preto 14040-900, Brazil
12
Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos-UFSCar, São Carlos 13565-905, Brazil
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors contributed equally to this work.
§
Membership of the IMMUNOCOVID Study Group is provided in the Acknowledgments.
Academic Editors: Carlos Fernandez-Patron, Eugenio Hardy and Myron R. Szewczuk
Biomolecules 2022, 12(5), 604; https://doi.org/10.3390/biom12050604
Received: 8 March 2022 / Revised: 8 April 2022 / Accepted: 14 April 2022 / Published: 19 April 2022
Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19. View Full-Text
Keywords: metalloproteinases; sHLA-G; sTREM-1; lipid peroxidation; COVID-19 metalloproteinases; sHLA-G; sTREM-1; lipid peroxidation; COVID-19
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MDPI and ACS Style

da Silva-Neto, P.V.; do Valle, V.B.; Fuzo, C.A.; Fernandes, T.M.; Toro, D.M.; Fraga-Silva, T.F.C.; Basile, P.A.; de Carvalho, J.C.S.; Pimentel, V.E.; Pérez, M.M.; Oliveira, C.N.S.; Rodrigues, L.C.; Bastos, V.A.F.; Tella, S.O.C.; Martins, R.B.; Degiovani, A.M.; Ostini, F.M.; Feitosa, M.R.; Parra, R.S.; Vilar, F.C.; Gaspar, G.G.; Rocha, J.J.R.d.; Feres, O.; Arruda, E.; Maruyama, S.R.; Russo, E.M.S.; Viana, A.L.; Santos, I.K.F.M.; Bonato, V.L.D.; Cardoso, C.R.B.; Tanus-Santos, J.E.; Donadi, E.A.; Faccioli, L.H.; Dias-Baruffi, M.; Fernandes, A.P.M.; Gerlach, R.F.; Sorgi, C.A.; on behalf of the IMMUNOCOVID Study Group. Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress. Biomolecules 2022, 12, 604. https://doi.org/10.3390/biom12050604

AMA Style

da Silva-Neto PV, do Valle VB, Fuzo CA, Fernandes TM, Toro DM, Fraga-Silva TFC, Basile PA, de Carvalho JCS, Pimentel VE, Pérez MM, Oliveira CNS, Rodrigues LC, Bastos VAF, Tella SOC, Martins RB, Degiovani AM, Ostini FM, Feitosa MR, Parra RS, Vilar FC, Gaspar GG, Rocha JJRd, Feres O, Arruda E, Maruyama SR, Russo EMS, Viana AL, Santos IKFM, Bonato VLD, Cardoso CRB, Tanus-Santos JE, Donadi EA, Faccioli LH, Dias-Baruffi M, Fernandes APM, Gerlach RF, Sorgi CA, on behalf of the IMMUNOCOVID Study Group. Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress. Biomolecules. 2022; 12(5):604. https://doi.org/10.3390/biom12050604

Chicago/Turabian Style

da Silva-Neto, Pedro V., Valéria B. do Valle, Carlos A. Fuzo, Talita M. Fernandes, Diana M. Toro, Thais F. C. Fraga-Silva, Patrícia A. Basile, Jonatan C. S. de Carvalho, Vinícius E. Pimentel, Malena M. Pérez, Camilla N. S. Oliveira, Lilian C. Rodrigues, Victor A. F. Bastos, Sandra O. C. Tella, Ronaldo B. Martins, Augusto M. Degiovani, Fátima M. Ostini, Marley R. Feitosa, Rogerio S. Parra, Fernando C. Vilar, Gilberto G. Gaspar, José J. R. da Rocha, Omar Feres, Eurico Arruda, Sandra R. Maruyama, Elisa M. S. Russo, Angelina L. Viana, Isabel K. F. M. Santos, Vânia L. D. Bonato, Cristina R. B. Cardoso, Jose E. Tanus-Santos, Eduardo A. Donadi, Lucia H. Faccioli, Marcelo Dias-Baruffi, Ana P. M. Fernandes, Raquel F. Gerlach, Carlos A. Sorgi, and on behalf of the IMMUNOCOVID Study Group. 2022. "Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress" Biomolecules 12, no. 5: 604. https://doi.org/10.3390/biom12050604

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