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The C-terminus of murine S100A9 protein inhibits hyperalgesia induced by the agonist peptide of protease-activated receptor 2 (PAR2).
Br J Pharmacol. 2006 Oct; 149(4):374-84.BJ

Abstract

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 (PAR2).

EXPERIMENTAL APPROACH

Mechanical and thermal hyperalgesia induced by PAR2 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 PAR2, in Kirsten virus-transformed kidney cells, transfected (KNRK-PAR2) or not (KNRK) with PAR2, 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 PAR2 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-PAR2 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 PAR2-induced nociceptive signal.

Authors+Show Affiliations

Laboratory of Pathophysiology, Butantan Institute, São Paulo, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16967049

Citation

Dale, C S., et al. "The C-terminus of Murine S100A9 Protein Inhibits Hyperalgesia Induced By the Agonist Peptide of Protease-activated Receptor 2 (PAR2)." British Journal of Pharmacology, vol. 149, no. 4, 2006, pp. 374-84.
Dale CS, Cenac N, Britto LR, et al. The C-terminus of murine S100A9 protein inhibits hyperalgesia induced by the agonist peptide of protease-activated receptor 2 (PAR2). Br J Pharmacol. 2006;149(4):374-84.
Dale, C. S., Cenac, N., Britto, L. R., Juliano, M. A., Juliano, L., Vergnolle, N., & Giorgi, R. (2006). The C-terminus of murine S100A9 protein inhibits hyperalgesia induced by the agonist peptide of protease-activated receptor 2 (PAR2). British Journal of Pharmacology, 149(4), 374-84.
Dale CS, et al. The C-terminus of Murine S100A9 Protein Inhibits Hyperalgesia Induced By the Agonist Peptide of Protease-activated Receptor 2 (PAR2). Br J Pharmacol. 2006;149(4):374-84. PubMed PMID: 16967049.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The C-terminus of murine S100A9 protein inhibits hyperalgesia induced by the agonist peptide of protease-activated receptor 2 (PAR2). AU - Dale,C S, AU - Cenac,N, AU - Britto,L R G, AU - Juliano,M A, AU - Juliano,L, AU - Vergnolle,N, AU - Giorgi,R, Y1 - 2006/09/11/ PY - 2006/9/13/pubmed PY - 2006/12/9/medline PY - 2006/9/13/entrez SP - 374 EP - 84 JF - British journal of pharmacology JO - Br J Pharmacol VL - 149 IS - 4 N2 - 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 (PAR2). EXPERIMENTAL APPROACH: Mechanical and thermal hyperalgesia induced by PAR2 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 PAR2, in Kirsten virus-transformed kidney cells, transfected (KNRK-PAR2) or not (KNRK) with PAR2, 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 PAR2 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-PAR2 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 PAR2-induced nociceptive signal. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/16967049/The_C_terminus_of_murine_S100A9_protein_inhibits_hyperalgesia_induced_by_the_agonist_peptide_of_protease_activated_receptor_2__PAR2__ L2 - https://doi.org/10.1038/sj.bjp.0706884 DB - PRIME DP - Unbound Medicine ER -