RESUMEN
PURPOSE: The concept of tissue-dependent cytokine hierarchy has been demonstrated in a number of diseases, but it has not been investigated in ophthalmic diseases. Here, we evaluated the functional hierarchy of interleukin-1ß (IL-1ß), IL-6, IL-17A, and tumor necrosis factor (TNF) in the induction of ocular inflammation. MATERIALS AND METHODS: We delivered adeno-associated virus (AAV) vectors expressing IL-1ß, IL-6, IL-17A, or TNF intravitreally in naïve C57/BL6 mice and compared and contrasted the inflammatory effects in the eye 5 weeks after AAV-mediated gene transfer. We also used an in vitro human system to test the effect of cytokines on barrier function. RESULTS: We found that IL-1ß had the highest ability to initiate ocular inflammation. The continuous overexpression of IL-1ß resulted in a significant upregulation of additional proinflammatory mediators in the eye. Using scanning laser ophthalmoscope and optical coherence tomography imaging techniques, we showed that a low dose of AAVIL-1ß was sufficient and was as pathogenic as a high dose of TNF in inducing vascular leakage, retinal degeneration, and cellular infiltration. Furthermore, only a marginal increase in IL-1ß was enough to cause cellular infiltration, thus confirming the highly pathogenic nature of IL-1ß in the eye. Contrary to our expectation, IL-6 or IL-17A had minimal or no effect in the eye. To examine the clinical relevance of our findings, we used an impedance assay to show that IL-1ß alone or TNF alone was able to cause primary human retinal endothelial cell barrier dysfunction in vitro. Again, IL-6 alone or IL-17A alone had no effect on barrier function; however, in the presence of IL-1ß or TNF, IL-17A but not IL-6 may provide additive proinflammatory effects. CONCLUSIONS: Our studies demonstrate the existence of a functional hierarchy of proinflammatory cytokines in the eye, and we show that IL-1ß is the most pathogenic when it is continuously expressed in the eye.
Asunto(s)
Citocinas/genética , Endoftalmitis/genética , Regulación de la Expresión Génica , ARN/genética , Animales , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Endoftalmitis/metabolismo , Endoftalmitis/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Inflamación/genética , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena en Tiempo Real de la Polimerasa , Arteria Retiniana/metabolismo , Arteria Retiniana/patología , Tomografía de Coherencia ÓpticaRESUMEN
The essential oil composition of three Zingiberaceae widely used as medicinal aromatic plants from S. Tomé and Príncipe: Aframomum danielli (Hook. f.) K. Schum., Curcuma longa L. and Zingiber officinale Rosc. was studied. Two samples of the essential oils from fruit of A. danielli and from rhizomes of the other two species, were obtained by hydrodistillation and analyzed by GC, GC-MS, and (13)C-NMR. The essential oil from fruits of A. danielli has been studied for the first time and was characterised by its high content of monoterpenes, with 1,8-cineole (25.5 - 34.4 %) the major constituent, followed by beta-pinene (14.1 - 15.2 %) and alpha-terpineol (9.9 - 12.1 %). Essential oils from the rhizomes of C. longa contained a lower content of ar-turmerone (4.0 - 12.8 %) than those reported in the literature for C. longa from other origins (24.7 - 31.4 %), whereas the results for Z. officinale essential oils were in accordance with the literature data. The essential oils of A. danielli and Z. officinale showed antimicrobial activity against all Gram-positive and Gram-negative bacteria tested, as well as against yeasts and filamentous fungi, using the agar diffusion method.
Asunto(s)
Antiinfecciosos/farmacología , Aceites Volátiles/química , Aceites de Plantas/química , Zingiberaceae/química , Antibacterianos , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Estructuras de las Plantas/química , Plantas Medicinales , PortugalRESUMEN
The composition and the antimicrobial activity of the bark oil of Croton stellulifer, an endemic and rare species of these islands (S. Tomé and Príncipe) are reported. Analysis was carried out by GC, GC/MS and 13C-NMR. The major constituents were alpha-phellandrene (15.4-18.6%), p-cymene (14.4-17.7%), linalool (12.0-12.6%) and alpha-pinene (8.1-9.1%). Kessane, a sesquiterpenoid oxide, not yet reported in the genus Croton, was identified by NMR. The essential oil of C. stellulifer was active against both bacterial and fungal strains, except Aspergillus niger.
Asunto(s)
Antiinfecciosos/química , Antiinfecciosos/farmacología , Euphorbiaceae/química , Aceites de Plantas/química , Aceites de Plantas/farmacología , Cromatografía de Gases , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad MicrobianaRESUMEN
The essential oils of OCIMUM CANUM, O. GRATISSIMUM and O. MINIMUM grown in S. Tomé, where they are used in Traditional Medicine mainly as febrifuge and for the treatment of respiratory diseases, were investigated. The essential oils were obtained from the aerial parts by hydrodistillation and subsequently analysed by GC, GC-MS and (13)C-NMR. (13)C-NMR SPECTROSCOPY proved to be an important tool, which can be very useful in the identification of most of the constituents. Major compounds in the volatile oil of O. GROTISSIMUM were thymol (48.1%) and P-cymene (12.5%). The essential oil of O. CANUM was characterized by its high content of TRANS-METHYL cinnamate (79.7%), whereas the most important oil constituent of O. MINIMUM was linalool (52.7%).
