Peripheral NLCR4 inflammasome participates in the genesis of acute inflammatory pain

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Pain; v. 156, n. 3, p. 451-459, MAR 2015.
• Citações Web of Science: 9

Resumo

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)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/19670-0 - Mecanismos envolvidos na fisiopatologia da artrite reumatóide, dor e sepse
• Beneficiário: Fernando de Queiroz Cunha
• Linha de fomento: Auxílio à Pesquisa - Temático