The C-terminus of murine S100A9 protein inhibits hyperalgesia induced by the agonist peptide of protease-activated receptor 2 (PAR(2))

The C-terminus of murine S100A9 protein inhibits hyperalgesia induced by the agonist peptide of protease-activated receptor 2 (PAR(2))

Autor Dale, C. S. Google Scholar
Cenac, N. Google Scholar
Britto, L. R. G. Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Vergnolle, N. Google Scholar
Giorgi, R. Google Scholar
Instituição Univ Calgary
Butantan Inst
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Resumo Background and purpose: S100A9 protein induces anti-nociception in rodents, in different experimental models of inflammatory pain. Herein, we investigated the effects of a fragment of the C-terminus of S100A9 (mS100A9p), on the hyperalgesia induced by serine proteases, through the activation of protease-activated receptor-2 (PAR(2)).Experimental approach: Mechanical and thermal hyperalgesia induced by PAR(2) agonists (SLIGRL-NH2 and trypsin) was measured in rats submitted to the paw pressure or plantar tests, and Egr-1 expression was determined by immunohistochemistry in rat spinal cord dorsal horn. Calcium flux in human embryonic kidney cells (HEK), which naturally express PAR(2), in Kirsten virus-transformed kidney cells, transfected (KNRK-PAR(2)) or not (KNRK) with PAR(2), and in mouse dorsal root ganglia neurons (DRG) was measured by fluorimetric methods.Key results: mS100A9p inhibited mechanical hyperalgesia induced by trypsin, without modifying its enzymatic activity. Mechanical and thermal hyperalgesia induced by SLIGRL-NH2 were inhibited by mS100A9p. SLIGRL-NH2 enhanced Egr-1 expression, a marker of nociceptor activation, and this effect was inhibited by concomitant treatment with mS100A9p. mS100A9p inhibited calcium mobilization in DRG neurons in response to the PAR(2) agonists trypsin and SLIGRL-NH2, but also in response to capsaicin and bradykinin, suggesting a direct effect of mS100A9 on sensory neurons. No effect on the calcium flux induced by trypsin or SLIGRL in HEK cells or KNRK-PAR(2) cells was observed.Conclusions and implications: These data demonstrate that mS100A9p interferes with mechanisms involved in nociception and hyperalgesia and modulates, possibly directly on sensory neurons, the PAR(2)-induced nociceptive signal.
Assunto S100A9
DRG neurons
HEK cells
KNRK-PAR(2) cells
Idioma Inglês
Data 2006-10-01
Publicado em British Journal of Pharmacology. London: Nature Publishing Group, v. 149, n. 4, p. 374-384, 2006.
ISSN 0007-1188 (Sherpa/Romeo, fator de impacto)
Editor Nature Publishing Group
Extensão 374-384
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000241520200005

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