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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Peripheral NLCR4 inflammasome participates in the genesis of acute inflammatory pain

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Author(s):
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Lopes, Alexandre H. [1] ; Talbot, Jhimmy [1] ; Silva, Rangel L. [1] ; Lima, Jonilson B. [1] ; Franca, Rafael O. [1] ; Verri, Jr., Waldiceu A. [2] ; Mascarenhas, Danielle P. [3] ; Ryffel, Bernhard [4, 5] ; Cunha, Fernando Q. [1, 3] ; Zamboni, Dario S. ; Cunha, Thiago M. [1]
Total Authors: 11
Affiliation:
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049900 Sao Paulo - Brazil
[2] Univ Estadual Londrina, Ctr Ciencias Biol, Dept Ciencias Patol, Londnna, Parana - Brazil
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell Biol, BR-14049900 Sao Paulo - Brazil
[4] Univ Orleans, Orleans - France
[5] CNRS, UMR7355, Expt & Mol Immunol & Neurogenet, F-45071 Orleans - France
Total Affiliations: 5
Document type: Journal article
Source: Pain; v. 156, n. 3, p. 451-459, MAR 2015.
Web of Science Citations: 9
Abstract

Inflammatory hyperalgesia is a complex process that depends on the sensitization of primary nociceptive neuron S triggered by proinflammatory mediators, such as interleukin 1 beta (IL-1 beta). Recently, the peripheral activation of caspase-1 (previously known as IL1-beta-converting enzyme) was implicated in the induction of acute inflammatory pain by promoting the processing of IL-1 beta from its precursor form, pro-IL-1 beta. Caspase-1 activation in several systems requires the assembly of an intracellular molecular platform called an inflammasome. Inflammasomes consist of 1 nucleotide-binding oligomerization domain-like receptor (NLR), the adapter molecule apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), and caspase-1. NLRP3 and NLRC4 inflammasomes are well described. However, the identity of the inflamniasome that is-involved in the peripheral activation of caspase-1 that accounts for acute inflammatory hyperalgesia has not been described. The present findings demonstrated that mice deficient in NLRC4 or ASC, but not in NLRP3, present reduced mechanical and thermal acute inflammatory hyperalgesia induced by carrageenan. The reduced hyperalgesia was accompanied by significant impairments in the levels of mature forms of IL-1 beta (p17) and caspase-1 (p20) compared to wild-type mice at the inflammatory site. Therefore, these results identified the inflammasome components NLRC4 and ASC as the molecular platform involved in the peripheral activation of caspase-1 and IL-1 beta maturation, which are responsible for the induction of acute inflammatory pain. In conclusion, our study -provides new therapeutic targets for the control of acute inflammatory pain. (AU)

FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis
Grantee:Fernando de Queiroz Cunha
Support Opportunities: Research Projects - Thematic Grants