Your browser doesn't support javascript.
loading
Suppression of inflammatory and infection responses in lung macrophages by eucalyptus oil and its constituent 1,8-cineole: Role of pattern recognition receptors TREM-1 and NLRP3, the MAP kinase regulator MKP-1, and NFκB.
Yadav, Niket; Chandra, Harish.
Afiliación
  • Yadav N; Microbial Pathogenesis and Immunotoxicology Laboratory, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
  • Chandra H; Microbial Pathogenesis and Immunotoxicology Laboratory, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
PLoS One ; 12(11): e0188232, 2017.
Article en En | MEDLINE | ID: mdl-29141025
ABSTRACT
Eucalyptus oil (EO) used in traditional medicine continues to prove useful for aroma therapy in respiratory ailments; however, there is a paucity of information on its mechanism of action and active components. In this direction, we investigated EO and its dominant constituent 1,8-cineole (eucalyptol) using the murine lung alveolar macrophage (AM) cell line MH-S. In an LPS-induced AM inflammation model, pre-treatment with EO significantly reduced (P ≤0.01or 0.05) the pro-inflammatory mediators TNF-α, IL-1 (α and ß), and NO, albeit at a variable rate and extent; 1,8-cineole diminished IL-1 and IL-6. In a mycobacterial-infection AM model, EO pre-treatment or post-treatment significantly enhanced (P ≤0.01) the phagocytic activity and pathogen clearance. 1,8-cineole also significantly enhanced the pathogen clearance though the phagocytic activity was not significantly altered. EO or 1,8-cineole pre-treatment attenuated LPS-induced inflammatory signaling pathways at various levels accompanied by diminished inflammatory response. Among the pattern recognition receptors (PRRs) involved in LPS signaling, the TREM pathway surface receptor (TREM-1) was significantly downregulated. Importantly, the pre-treatments significantly downregulated (P ≤0.01) the intracellular PRR receptor NLRP3 of the inflammasome, which is consistent with the decrease in IL-1ß secretion. Of the shared downstream signaling cascade for these PRR pathways, there was significant attenuation of phosphorylation of the transcription factor NF-κB and p38 (but increased phosphorylation of the other two MAP kinases, ERK1/2 and JNK1/2). 1,8-cineole showed a similar general trend except for an opposite effect on NF-κB and JNK1/2. In this context, either pre-treatment caused a significant downregulation of MKP-1 phosphatase, a negative regulator of MAPKs. Collectively, our results demonstrate that the anti-inflammatory activity of EO and 1,8-cineole is modulated via selective downregulation of the PRR pathways, including PRR receptors (TREM-1 and NLRP3) and common downstream signaling cascade partners (NF-κB, MAPKs, MKP-1). To our knowledge, this is the first report on the modulatory role of TREM-1 and NLRP3 inflammasome pathways and the MAPK negative regulator MKP-1 in context of the anti-inflammatory potential of EO and its constituent 1,8-cineole.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Aceites de Plantas / FN-kappa B / Macrófagos Alveolares / Ciclohexanoles / Monoterpenos / Eucalyptus / Fosfatasa 1 de Especificidad Dual / Proteína con Dominio Pirina 3 de la Familia NLR / Receptor Activador Expresado en Células Mieloides 1 / Inflamación Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Aceites de Plantas / FN-kappa B / Macrófagos Alveolares / Ciclohexanoles / Monoterpenos / Eucalyptus / Fosfatasa 1 de Especificidad Dual / Proteína con Dominio Pirina 3 de la Familia NLR / Receptor Activador Expresado en Células Mieloides 1 / Inflamación Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos