RESUMO
Lavender essential oil (Lvn) has anti-inflammatory effects in an ovalbumin-sensitized murine model of asthma, and inhibits inflammatory cell infiltration into the lungs. The anti-inflammatory effects of Lvn on cell adhesion molecules are not clear. Here we evaluated the effects of Lvn and its main constituents, linalyl acetate (LA) and linalool (LO), on the expression of tumor necrosis factor-alpha (TNF-α)-induced cell adhesion molecules in murine brain endothelial bEnd.3 cells and human umbilical vein endothelial cells (HUVECs). The bEnd.3 cells were treated with Lvn, LA, or LO and subsequently stimulated with TNF-α. The mRNA expression levels of cell adhesion molecules were detected using RT-PCR. E-selectin and P-selectin protein and phosphorylated-NF-κB p65 were detected by western blotting. The effects of Lvn on HUVECs were measured by RT-PCR. In bEnd.3 cells, Lvn and LA suppressed TNF-α-induced E-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and phosphorylated-NF-κB p65 in the nucleus; LO did not suppress P-selectin or phosphorylated-NF-κB p65. Lvn inhibited TNF-α-induced E-selectin mRNA in HUVECs. These results indicate that Lvn and LA inhibit TNF-α-induced cell adhesion molecules in endothelial cells through the suppression of NF-κB activation. Consequently, Lvn or other essential oils including LA may be useful as alternative anti-inflammatory medicines.
Assuntos
Moléculas de Adesão Celular/análise , Células Endoteliais/efeitos dos fármacos , Monoterpenos/farmacologia , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Monoterpenos Acíclicos , Animais , Moléculas de Adesão Celular/genética , Células Endoteliais/química , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lavandula , Camundongos , NF-kappa B/fisiologia , Óleos Voláteis/análise , Óleos de Plantas/análise , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
AIMS: Lavender essential oil (Lvn) has been reported to have anti-inflammatory effects. Bronchial asthma is characterized by bronchial allergic inflammation with airway remodeling. Therefore, we evaluated the anti-inflammatory effect of Lvn on experimentally induced bronchial asthma in a murine model. MAIN METHODS: BALB/c mice were sensitized by an intraperitoneal injection of ovalbumin (OVA) at days 0 and 14, and subsequently challenged with nebulized OVA on days 28-30 (Control-Asthma group). Mice in the treatment group inhaled Lvn on days 14-31 (Lvn-Asthma group). The allergic inflammatory response was determined on days 32 and 33. KEY FINDINGS: An increase in airway resistance was inhibited in the Lvn-Asthma group than in the Control-Asthma group. The Lvn-Asthma group showed lower total cell numbers and eosinophils in bronchoalveolar lavage (BAL) fluids and peribronchial and perivascular tissues when compared with the Control-Asthma group. The Lvn-Asthma group also had less mucin hyperplasia than the Control-Asthma group. Furthermore, the Lvn-Asthma group showed lower interleukin (IL)-5 and IL-13 cytokine levels in BAL fluids, as well as reduced IL-4 and IL-5 mRNA expression in lung tissue, compared with the Control-Asthma group and determined by FlowCytomix and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. In addition, Lvn inhalation reduced Muc5b mRNA expression in the lungs without significantly changing the expression of Muc5ac mRNA. SIGNIFICANCE: Lvn inhibits allergic inflammation and mucous cell hyperplasia with suppression of T-helper-2 cell cytokines and Muc5b expression in a murine model of asthma. Consequently, Lvn may be useful as an alternative medicine for bronchial asthma.
Assuntos
Anti-Inflamatórios/farmacologia , Asma/tratamento farmacológico , Hiperplasia/tratamento farmacológico , Inflamação/tratamento farmacológico , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Administração por Inalação , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Anti-Inflamatórios/administração & dosagem , Asma/imunologia , Asma/patologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Feminino , Inflamação/imunologia , Inflamação/patologia , Interleucina-13/metabolismo , Interleucina-5/metabolismo , Lavandula , Camundongos , Camundongos Endogâmicos BALB C , Mucina-5B/genética , Óleos Voláteis/administração & dosagem , Ovalbumina/imunologia , Óleos de Plantas/administração & dosagem , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Th2/imunologia , Fatores de TempoRESUMO
ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an inflammatory-induced gene. We have previously reported that ADAMTS1 was strongly but transiently expressed in the infarcted heart. In this study, we investigated whether a 3'-untranslated region (UTR) affects the mRNA stability of this gene. When stimulated with tissue necrosis factor (TNF)-alpha, the expression level of ADAMTS1 mRNA rapidly increased, but the induction of ADAMTS1 mRNA peaked at 6h after stimulation, after which the expression levels of ADAMTS1 mRNA decreased. The 3'-UTR ADAMTS1 mRNA contains multiple adenine and uridine-rich elements, suggesting that the 3'-UTR may regulate gene stability. The addition of actinomycin D, an RNA synthesis inhibitor, demonstrated the decay of induced ADAMTS1 mRNA by TNF-alpha. Furthermore, a region containing multiple AUUUA motifs within the ADAMTS1 3'-UTR destabilized transfected Enhanced Green Fluorescence Protein (EGFP) mRNA expression. These results demonstrated that the ADAMTS1 3'-UTR may regulate the expression of ADAMTS1 mRNA.
Assuntos
Regiões 3' não Traduzidas/genética , Proteínas ADAM , Estabilidade de RNA/genética , RNA Mensageiro , Proteínas ADAM/genética , Proteínas ADAM/metabolismo , Proteína ADAMTS1 , Animais , Sequência de Bases , Células COS , Chlorocebus aethiops , Dactinomicina/metabolismo , Humanos , Camundongos , Dados de Sequência Molecular , Inibidores da Síntese de Ácido Nucleico/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: The relationship between serum fatty acid levels and the extent of coronary plaques and calcification was examined in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The serum levels of the n-3 polyunsaturated fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) and the n-6 polyunsaturated fatty acids (arachidonic acid (AA) and dihomo-gamma-linolenic acid (DGLA)) were determined using gas chromatography on admission of 95 consecutive patients with their first AMI and 17 controls. Using multidetector-row computed tomography, soft plaques and calcification lesions were scored according to the extent of coronary involvement. Serum logarithmic transformed (log) EPA and logDHA levels were inversely correlated with soft plaque scores (r=-0.546, p<0.0001 and r=-0.377, p<0.0001, respectively). Serum logAA and logDGLA levels were not significantly correlated with soft plaque scores. Serum logEPA and logDHA levels were significantly, but weakly, correlated with calcification scores. Multivariate analysis with clinical characteristics and risk factors selected serum n-3 polyunsaturated fatty acid levels as independent factors associated with the extent of coronary soft plaques. CONCLUSION: The present study demonstrates a significant correlation between serum n-3 polyunsaturated fatty acid levels and the extent of coronary soft plaques and calcification in AMI patients.
Assuntos
Calcinose/sangue , Doença da Artéria Coronariana/sangue , Ácidos Graxos Insaturados/sangue , Infarto do Miocárdio/sangue , Idoso , Calcinose/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Phosphoenolpyruvate carboxykinase (PEPCK) is one of the key regulatory enzymes in gluconeogenesis. In human liver, PEPCK is about equally distributed in both cytosol (PEPCK-1) and mitochondria (PEPCK-2). The human pepck2 gene and cDNA have been reported, but the cloning of the promoter region of the pepck2 gene has not been elucidated yet. We isolated and characterized human genomic P1-artificial chromosome (PAC) clones carrying the human pepck2 gene promoter. The oligocapping method revealed that the transcriptional start point (tsp) of the human pepck2 gene is located at 97 bp upstream of the first adenine residue of the translation start site. We also determined the nucleotide sequence to 1819 bp upstream of tsp. Sequence analysis of this region revealed that it contained several potential regulatory elements, including five GC boxes and three CCAAT boxes. Reporter analysis using transient transfection with firefly luciferase synthetic gene indicated 5' flanking region up to 822 bp, and 317 bp upstream of tsp had transcriptional activity. These results suggest that these regions of the human pepck2 gene play an important role for its expression.