Transmembrane TNF-α is sufficient for articular inflammation and hypernociception in a mouse model of gout.
Eur J Immunol
; 46(1): 204-11, 2016 Jan.
Article
en En
| MEDLINE
| ID: mdl-26449770
ABSTRACT
Gout manifests as recurrent episodes of acute joint inflammation and pain due to the deposition of monosodium urate (MSU) crystals within the affected tissue in a process dependent on NLRP3 inflammasome activation. The synthesis, activation, and release of IL-1ß are crucial for MSU-induced inflammation. The current study evaluated the mechanism by which TNF-α contributed to MSU-induced inflammation. Male C57BL/6J or transgenic mice were used in this study and inflammation was induced by the injection of MSU crystals into the joint. TNF-α was markedly increased in the joint after the injection of MSU. There was inhibition in the infiltration of neutrophils, production of CXCL1 and IL-1ß, and decreased hypernociception in mice deficient for TNF-α or its receptors. Pharmacological blockade of TNF-α with Etanercept or pentoxyfylline produced similar results. Mechanistically, TNF-α blockade resulted in lower amounts of IL-1ß protein and pro-IL-1ß mRNA transcripts in joints. Gene-modified mice that express only transmembrane TNF-α had an inflammatory response similar to that of WT mice and blockade of soluble TNF-α (XPro™1595) did not decrease MSU-induced inflammation. In conclusion, TNF-α drives expression of pro-IL-1ß mRNA and IL-1ß protein in experimental gout and that its transmembrane form is sufficient to trigger MSU-induced inflammation in mice.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factor de Necrosis Tumoral alfa
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Gota
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Hiperalgesia
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Inflamación
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Brasil