title: Gamma-Terpinene Modulation of LPS-Stimulated Macrophages is Dependent on the PGE2/IL-10 Axis.
abstract: Gamma-terpinene is a monoterpene present in the essential oils of several plants, including those from theEucalyptusgenus. This molecule was recently described as anti-inflammatory and microbiocidal, but little is known about the mechanisms behind its effects. The aim of the present study was to investigate the effect of gamma-terpinene on the lipopolysaccharide-induced production of cytokines by murine peritoneal macrophages. Gamma-terpinene treatment was found to reduce the production of proinflammatory cytokines, such as interleukin-1βand interleukin-6, and enhance that of the anti-inflammatory cytokine interleukin-10. This was accompanied by increased levels of the enzyme cycloxygenase-2 and its product, the lipid mediator prostaglandin E2. Inhibition of cycloxygenase-2 with nimesulide abolished the potentiating effect of gamma-terpinene on interleukin-10 production. Moreover, nimesulide treatment also abrogated the inhibitory effect of gamma-terpinene on interleukin-1βand interleukin-6. Furthermore, in macrophages from mice deficient in the interleukin-10 gene, gamma-terpinene failed to inhibit interleukin-1βand interleukin-6 production. These results suggest that this monoterpene promotes the prostaglandin E2/interleukin-10 axis, which inhibits the production of these proinflammatory cytokines.
authors.affiliation: Laboratory of Immunopharmacology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brasil.
authors.forename: Theresa R
authors.initials: TR
authors.lastname: Ramalho
authors.affiliation: Laboratory of Immunopharmacology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brasil.
authors.forename: Luciano R
authors.initials: LR
authors.lastname: Filgueiras
authors.affiliation: Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Maria Talita
authors.initials: MT
authors.lastname: Pacheco de Oliveira
authors.affiliation: Natural Synthetic and Bioactive Products Post-graduation Program, Health Sciences Center, Federal University of Paraíba, João Pessoa, Paraíba, Brasil.
authors.forename: Ana Luisa de Araujo
authors.initials: AL
authors.lastname: Lima
authors.affiliation: Laboratory of Immunopharmacology, Department de Physiology and Pathology, Federal University of Paraíba, João Pessoa, Paraíba, Brasil.
authors.forename: Claudio Roberto
authors.initials: CR
authors.lastname: Bezerra-Santos
authors.affiliation: Laboratory of Immunopharmacology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brasil.
authors.forename: Sonia
authors.initials: S
authors.lastname: Jancar
authors.affiliation: Natural Synthetic and Bioactive Products Post-graduation Program, Health Sciences Center, Federal University of Paraíba, João Pessoa, Paraíba, Brasil.
authors.forename: Marcia Regina
authors.initials: MR
authors.lastname: Piuvezam
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000081005:Cyclohexane Monoterpenes; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D039821:Monoterpenes / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000081005:Cyclohexane Monoterpenes; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; C556062:IL10 protein, mouse; D008070:Lipopolysaccharides; D039821:Monoterpenes; D013449:Sulfonamides; D016753:Interleukin-10; D018664:Interleukin-12; C018669:gamma-terpinene; D015232:Dinoprostone; C012655:nimesulide