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Open Access Research

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

Thiago M Cunha1*, Jhimmy Talbot1, Larissa G Pinto1, Silvio M Vieira1, Guilherme R Souza1, Ana T Guerrero1, Fabiane Sonego1, Waldiceu A Verri13, Dario S Zamboni2, Sergio H Ferreira1 and Fernando Q Cunha1*

Author Affiliations

1 Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirao Preto, SP, Brazil

2 Department of Cell Biology Faculty of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirao Preto, SP Brazil

3 Universidade Estadual de Londrina, Centro de Ciências Biológicas, Departamento de Ciências Patológicas. Rodovia Celso Garcia Cid PR - 445 Km 379, 86051-970 - Londrina, PR Brasil

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Molecular Pain 2010, 6:63  doi:10.1186/1744-8069-6-63

Published: 4 October 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.