A study on inhibition of inflammation via p75TNFR signaling pathway activation in mice with traumatic brain injury.
J Surg Res
; 182(1): 127-33, 2013 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-22935315
OBJECTIVE: To investigate the effects of and mechanisms underlying the activation of the p75 tumor necrosis factor receptor (p75TNFR) signaling pathway in inflammatory responses in mice with traumatic brain injury. METHODS: We first generated hybridomas that produced antibodies specific for p75TNFR, by inoculating BALB/c mice with antigenic peptides derived from mouse p75TNFR, which is critical to the binding of tumor necrosis factor-alpha (TNF-α) and p75TNFR. The isotype, epitope, titer, specificity, and affinity constant of monoclonal antibodies (mAbs) were determined using commercial kits and enzyme-linked immunosorbent assay. We then screened the agonist antibody via L929 cytotoxicity assay. The levels of inflammatory factors were detected in C57BL/6 mice with traumatic brain injury and then the mice were injected with either saline (control) or p75TNFR agonist mAb. Furthermore, we investigated the effects of p75TNFR agonist mAb on p38MAPK and nuclear factor-κB signals. RESULTS: Seven mAbs against p75TNFR were generated. Among them, the mAb D8F2 could markedly enhance the cytotoxicity of TNF-α on L929 cells. In a traumatic brain injury model, D8F2 could inhibit the levels of inflammatory factors and downregulate RNA transcription of these factors by suppressing the activation of p38 mitogen-activated protein kinase and nuclear factor-κB. CONCLUSION: The mAb D8F2 could inhibit posttraumatic inflammatory responses effectively. In this study, we developed an agonist anti-mouse p75TNFR mAb, which may be used in the future to devise new strategies for the clinical treatment of inflammation after trauma.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Lesiones Encefálicas
/
Transducción de Señal
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Receptores Tipo II del Factor de Necrosis Tumoral
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Encefalitis
/
Anticuerpos Monoclonales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Surg Res
Año:
2013
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos