Fluorofenidone attenuates interleukin-1ß production by interacting with NLRP3 inflammasome in unilateral ureteral obstruction.
Nephrology (Carlton)
; 23(6): 573-584, 2018 Jun.
Article
em En
| MEDLINE
| ID: mdl-28437591
ABSTRACT
AIM:
We explored whether Fluorofenidone reduced interleukin-1ß (IL-1ß) production by interacting with NLRP3 inflammasome in unilateral ureteral obstruction (UUO).METHODS:
Ureteral obstruction rats were treated with Fluorofenidone (500 mg/kg per day) for 3, 7 days. Morphologic analysis and leukocytes infiltration were assessed in ligated kidneys. Furthermore, plasmids of NLRP3, ASC, pro-Caspase-1, pro-IL-1ß were co-transfected into 293 T cells, and then treated with Fluorofenidone (2 mM). The expression of NLRP3, ASC, pro-caspase-1, cleavage caspase-1, pro-IL-1ß and cleavage IL-1ß were measured by Western blot or real-time PCR in vivo and in vitro. Moreover the interaction of NLRP3 inflammasome-assembly was detected by co-immunoprecipitation and confocal immunofluorescence.RESULTS:
Fluorofenidone treatment significantly attenuated renal fibrosis and leukocytes infiltration in UUO model. Fluorofenidone had no effect on the expression of pro-IL-1ß. Interestingly, Fluorofenidone inhibited the activation of NLRP3 inflammasome, downregulated Caspase-1 levels and thereby decreased the cleavage of pro-IL-1ß into IL-1ß in vivo and in vitro. Fluorofenidone treatment distinctively weakened the interaction between NLRP3 and ASC, as well as ASC and pro-Caspase-1 in vivo. However, Fluorofenidone treatment only significantly weakened the interaction between ASC and pro-Caspase-1 in co-transfected 293 T cells.CONCLUSION:
Fluorofenidone serves as a novel anti-inflammatory agent that attenuates IL-1ß production in UUO model by interacting with NLRP3 inflammasome.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridonas
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Obstrução Ureteral
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Interleucina-1beta
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Inflamassomos
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Proteína 3 que Contém Domínio de Pirina da Família NLR
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Rim
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Anti-Inflamatórios
/
Nefrite
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Nephrology (Carlton)
Assunto da revista:
NEFROLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China