Main pathways of action of Brazilian red propolis on the modulation of neutrophils migration in the inflammatory process.
BACKGROUND
Brazilian propolis is popularly used as treatment for different diseases including the ones with inflammatory origin. Brazilian red propolis chemical profile and its anti-inflammatory properties were recently described however, its mechanism of action has not been investigated yet.


OBJECTIVE
Elucidate Brazilian red propolis major pathways of action on the modulation of neutrophil migration during the inflammatory process.


METHODS
The ethanolic extract of propolis (EEP) activity was investigated for neutrophil migration into the peritoneal cavity, intravital microscopy (rolling and adhesion of leukocytes), quantification of cytokines TNF-α, IL-1β and chemokines CXCL1/KC, CXCL2/MIP-2, neutrophil chemotaxis induced by CXCL2/MIP-2, calcium influx and CXCR2 expression on neutrophils.


RESULTS
EEP at 10mg/kg prevented neutrophil migration into peritoneal cavity (p < 0.05), reduced leukocyte rolling and adhesion on the mesenteric microcirculation (p < 0.05) and inhibited the release TNF-α, IL-1β, CXCL1/KC and CXCL2/MIP-2 (p < 0.05). EEP at 0.01, 0.1 and 1µg/ml reduced the CXCL2/MIP-2-induced neutrophils chemotaxis (p < 0.05) without affect cell viability (p > 0.05).EEP at 1µg/ml decreased the calcium influx induced by CXCL2/MIP-2 (p<0.05). On the other hand, none of EEP concentrations tested altered CXCR2 expression by neutrophils (p>0.05).


CONCLUSIONS
Brazilian red propolis appears as a promising anti-inflammatory natural product which mechanism seems to be by reducing leukocyte rolling and adhesion; TNF-α, IL-1β, CXCL1/KC and CXCL2/MIP-2 release; CXCL2/MIP-2-induced chemotaxis and calcium influx.
Dental Research Division, Guarulhos University, Guarulhos, SP, Brazil; Department of Physiological Sciences, School of Dentistry of Piracicaba, University of Campinas, 901 Limeira Ave., 13414 903 Piracicaba, SP, Brazil. Electronic address: bruno.silva@prof.ung.br.
Bruno
B
Bueno-Silva
Department of Physiological Sciences, School of Dentistry of Piracicaba, University of Campinas, 901 Limeira Ave., 13414 903 Piracicaba, SP, Brazil.
Marcelo
M
Franchin
Laboratory of Nanobiotechnology and Molecular Biology, Institute of Genetics and Biochemistry Federal University of Uberlândia, Uberlândia, MG, Brazil.
Claudiney de Freitas
CF
Alves
Department of Physiological Sciences, School of Dentistry of Piracicaba, University of Campinas, 901 Limeira Ave., 13414 903 Piracicaba, SP, Brazil.
Carina
C
Denny
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
David Fernando
DF
Colón
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Thiago Mattar
TM
Cunha
Department of Agri-Food industry, Food and Nutrition, "Luiz de Queiroz" College of Agriculture, University of São Paulo, Piracicaba, SP, Brazil.
Severino Matias
SM
Alencar
Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, Campinas, SP, Brazil.
Marcelo Henrique
MH
Napimoga
Department of Physiological Sciences, School of Dentistry of Piracicaba, University of Campinas, 901 Limeira Ave., 13414 903 Piracicaba, SP, Brazil.
Pedro Luiz
PL
Rosalen
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001938:Brazil; D002465:Cell Movement / Q000187:drug effects; D054426:Chemokine CXCL2 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011429:Propolis / Q000494:pharmacology*; D054367:Receptors, CXCR3 / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; C515188:Cxcr3 protein, mouse; D016207:Cytokines; D054367:Receptors, CXCR3; D011429:Propolis
Brazilian red propolis; Cytokines; Inflammation; Neutrophils