Caspase-1 inhibition by YVAD generates tregs pivoting IL-17 to IL-22 response in ß-glucan induced airway inflammation.
Immunopharmacol Immunotoxicol
; 44(3): 316-325, 2022 Jun.
Article
em En
| MEDLINE
| ID: mdl-35225131
ABSTRACT
BACKGROUND:
During Aspergillus fumigatus mediated lung inflammation, NLRP3 inflammasome is rapidly activated that aggravates IL-1ß production contributing to lung inflammation. Previously, we have shown the protective role of SYK-1 inhibition in inhibiting inflammasome activation during lung inflammation. In the current manuscript, we explored the protective role of direct caspase-1 inhibition during ß-glucan-induced lung inflammation.METHODS:
We have mimicked the lung inflammation by administering intranasal ß-glucan in mice model. YVAD was used for caspase-1 inhibition.RESULTS:
We have shown that caspase-1 inhibition by YVAD did not alter inflammasome independent inflammatory cytokines, while it significantly reduced inflammasome activation and IL-1ß secretion. Caspase-1 inhibited bone marrow derived dendritic cells (BMDCs), co-cultured with T cells showed decreased T-cell proliferation and direct them to secrete high TGF-ß and IL-10 compared to the T cells co-cultured with ß-glucan primed dendritic cells. Caspase-1 inhibition in BMDCs also induced IL-22 secretion from CD4+T cells. Caspase-1 inhibition in intranasal ß-glucan administered mice showed decreased tissue damage, immune cell infiltration and IgA secretion compared to control mice. Further, splenocytes challenged with ß-glucan show high IL-10 secretion and increased FOXp3 and Ahr indicating an increase in regulatory T cells on caspase-1 inhibition.CONCLUSION:
Caspase-1 inhibition can thus be an attractive target to prevent inflammation mediated tissue damage during Aspergillus fumigatus mouse model and can be explored as an attractive therapeutic strategy.HIGHLIGHTSCaspase-1 inhibition protects lung damage from inflammation during ß-glucan exposureCaspase-1 inhibition in dendritic cells decreases IL-1ß production resulting in decreased pathogenic Th17Caspase-1 inhibition promotes regulatory T cells thereby inhibiting lung inflammation.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
/
Beta-Glucanas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Immunopharmacol Immunotoxicol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
/
TOXICOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Índia