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Open Access 01-12-2010 | Research

Caspase-1 is involved in the genesis of inflammatory hypernociception by contributing to peripheral IL-1β maturation

Authors: Thiago M Cunha, Jhimmy Talbot, Larissa G Pinto, Silvio M Vieira, Guilherme R Souza, Ana T Guerrero, Fabiane Sonego, Waldiceu A Verri Jr, Dario S Zamboni, Sergio H Ferreira, Fernando Q Cunha

Published in: Molecular Pain | Issue 1/2010

Abstract

Background

Caspase-1 is a cysteine protease responsible for the processing and secretion of IL-1β and IL-18, which are closely related to the induction of inflammation. However, limited evidence addresses the participation of caspase-1 in inflammatory pain. Here, we investigated the role of caspase-1 in inflammatory hypernociception (a decrease in the nociceptive threshold) using caspase-1 deficient mice (casp1-/-).

Results

Mechanical inflammatory hypernociception was evaluated using an electronic version of the von Frey test. The production of cytokines, PGE₂ and neutrophil migration were evaluated by ELISA, radioimmunoassay and myeloperoxidase activity, respectively. The interleukin (IL)-1β and cyclooxygenase (COX)-2 protein expression were evaluated by western blotting. The mechanical hypernociception induced by intraplantar injection of carrageenin, tumour necrosis factor (TNF)α and CXCL1/KC was reduced in casp1-/- mice compared with WT mice. However, the hypernociception induced by IL-1β and PGE₂ did not differ in WT and casp1-/- mice. Carrageenin-induced TNF-α and CXCL1/KC production and neutrophil recruitment in the paws of WT mice were not different from casp1-/- mice, while the maturation of IL-1β was reduced in casp1-/- mice. Furthermore, carrageenin induced an increase in the expression of COX-2 and PGE₂ production in the paw of WT mice, but was reduced in casp1-/- mice.

Conclusion

These results suggest that caspase-1 plays a critical role in the cascade of events involved in the genesis of inflammatory hypernociception by promoting IL-1β maturation. Because caspase-1 is involved in the induction of COX-2 expression and PGE₂ production, our data support the assertion that caspase-1 is a key target to control inflammatory pain.

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Title: Caspase-1 is involved in the genesis of inflammatory hypernociception by contributing to peripheral IL-1β maturation
Authors: Thiago M Cunha
Jhimmy Talbot
Larissa G Pinto
Silvio M Vieira
Guilherme R Souza
Ana T Guerrero
Fabiane Sonego
Waldiceu A Verri Jr
Dario S Zamboni
Sergio H Ferreira
Fernando Q Cunha
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2010
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-6-63

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Caspase-1 is involved in the genesis of inflammatory hypernociception by contributing to peripheral IL-1β maturation

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

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