Serum amyloid a1/toll-like receptor-4 Axis, an important link between inflammation and outcome of TBI patients
Author
Farré-Alins, Víctor; Palomino-Antolín, Alejandra; Narros-Fernández, Paloma; Lopez-Rodriguez, Ana Belen; Decouty-Perez, Céline; Muñoz-Montero, Alicia; Zamorano-Fernández, Jorge; Mansilla-Fernández, Beatriz; Giner-García, Javier; García-Feijoo, Pablo; Sáez-Alegre, Miguel; Palpán-Flores, Alexis J.; Roda-Frade, José María; Carabias, Cristina S.; Rosa, Juliana M.; Civantos-Martín, Belén; Yus-Teruel, Santiago; Gandía Juan, Luis
Entity
UAM. Departamento de FarmacologíaPublisher
MDPIDate
2021-05-25Citation
10.3390/biomedicines9060599
Biomedicines 9.6 (2021): 599
ISSN
2227-9059DOI
10.3390/biomedicines9060599Funded by
This work was supported by grants from Fundación Mutua Madrileña and Fondo de Investigaciones Sanitarias (FIS) (ISCIII/FEDER) (Programa Miguel Servet CP14/00008; CPII19/00005; PI16/00735; PI19/00082) to JE, RYC2019-026870-I to JMR and PI18/01387 to ALProject
Gobierno de España. PI18/01387; Gobierno de España. PI16/00735; Gobierno de España. PI19/00082Editor's Version
https://doi.org/10.3390/biomedicines9060599Subjects
Biomarkers; Immunomodulation; Neuroinflammation; Prognosis; Traumatic brain injury; Farmacia; MedicinaRights
© 2021 by the authorsAbstract
Traumatic brain injury (TBI) is one of the leading causes of mortality and disability world-wide without any validated biomarker or set of biomarkers to help the diagnosis and evaluation of the evolution/prognosis of TBI patients. To achieve this aim, a deeper knowledge of the biochemical and pathophysiological processes triggered after the trauma is essential. Here, we identified the serum amyloid A1 protein-Toll-like receptor 4 (SAA1-TLR4) axis as an important link between inflammation and the outcome of TBI patients. Using serum and mRNA from white blood cells (WBC) of TBI patients, we found a positive correlation between serum SAA1 levels and injury severity, as well as with the 6-month outcome of TBI patients. SAA1 levels also correlate with the presence of TLR4 mRNA in WBC. In vitro, we found that SAA1 contributes to inflammation via TLR4 activation that releases inflammatory cytokines, which in turn increases SAA1 levels, establishing a positive proinflammatory loop. In vivo, post-TBI treatment with the TLR4-antagonist TAK242 reduces SAA1 levels, improves neurobehavioral outcome, and prevents blood–brain barrier disruption. Our data support further evaluation of (i) post-TBI treatment in the presence of TLR4 inhibition for limiting TBI-induced damage and (ii) SAA1-TLR4 as a biomarker of injury progression in TBI patients
Files in this item
Google Scholar:Farré-Alins, Víctor
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Palomino-Antolín, Alejandra
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Narros-Fernández, Paloma
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Lopez-Rodriguez, Ana Belen
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Decouty-Perez, Céline
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Muñoz-Montero, Alicia
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Zamorano-Fernández, Jorge
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Mansilla-Fernández, Beatriz
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Giner-García, Javier
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García-Feijoo, Pablo
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Sáez-Alegre, Miguel
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Palpán-Flores, Alexis J.
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Roda-Frade, José María
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Carabias, Cristina S.
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Rosa, Juliana M.
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Civantos-Martín, Belén
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Yus-Teruel, Santiago
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Gandía Juan, Luis
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Lagares, Alfonso
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Hernández-García, Borja J.
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Egea, Javier
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