Limonene suppresses lipopolysaccharide-induced production of nitric oxide, prostaglandin E2, and pro-inflammatory cytokines in RAW 264.7 macrophages.
ABSTRACT The monoterpene D-limonene and its metabolites have been shown to exert chemopreventive and chemotherapeutic effects against different tumours in animal models and clinical trials. However, it is unknown whether these compounds modulate the inflammatory response in RAW 264.7 macrophage cells. The present study was therefore designed to elucidate the pharmacological and biological effects of D-limonene on the production of pro-inflammatory cytokines and inflammatory mediators in macrophages. The results indicate that D-limonene is an effective inhibitor of lipopolysaccharide (LPS)-induced NO and prostaglandin E(2) production in RAW 264.7 cells. These inhibitory effects of D-limonene included dose-dependent decreases in the expression of iNOS and COX-2 proteins. To evaluate the inhibitory effects of D-limonene on other cytokines, we also measured TNF-alpha, IL-1beta, and IL-6 levels in the cell supernatants of LPS-stimulated RAW 264.7 macrophages by enzyme-linked immunosorbent assay. In these assays, D-limonene decreased the expression of TNF-alpha, IL-1beta, and IL-6 in a dose-dependent manner. To assess the suitability of D-limonene for cosmetic applications, we also performed 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assays on HaCaT keratinocytes. D-limonene did not display any cytotoxicity in these assays. From these results, we suggest that D-limonene may be considered a potential anti-inflammatory candidate.
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ABSTRACT: Lipopolysaccharide (LPS) from Gram-negative bacteria is one of the most potent innate immune-activating stimuli known. Here we review the current understanding of LPS effects on human monocyte and macrophage function. We provide an overview of LPS signal transduction with attention given to receptor cooperativity and species differences in LPS responses, as well as the role of tyrosine phosphorylation and lysine acetylation in signalling. We also review LPS-regulated transcription, with emphasis on chromatin remodeling and primary versus secondary transcriptional control mechanisms. Finally, we review the regulation and function of LPS-inducible cytokines produced by human monocytes and macrophages including TNFα, the IL-1 family, IL-6, IL-8, the IL-10 family, the IL-12 family, IL-15 and TGFβ.Critical Reviews in Immunology 01/2011; 31(5):379-446. · 3.32 Impact Factor
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ABSTRACT: Various compounds in present human breath have long been loosely associated with pathological states (including acetone smell in uncontrolled diabetes). Only recently, however, the precise measurement of exhaled volatile organic compounds (VOCs) and aerosolized particles was made possible at extremely low concentrations by advances in several analytical methodologies, described in detail in the international literature and each suitable for specific subsets of exhaled compounds. Exhaled gases may be generated endogenously (in the pulmonary tract, blood, or peripheral tissues), as metabolic by-products of human cells or colonizing micro-organisms, or may be inhaled as atmospheric pollutants; growing evidence indicates that several of these molecules have distinct cell-to-cell signaling functions. Independent of origin and physiological role, exhaled VOCs are attractive candidates as biomarkers of cellular activity/metabolism, and could be incorporated in future non-invasive clinical testing devices. Indeed, several recent studies reported altered exhaled gas profiles in dysmetabolic conditions and relatively accurate predictions of glucose concentrations, at least in controlled experimental conditions, for healthy and diabetic subjects over a broad range of glycemic values. Optimization of this methodology and validation in large-scale trials under a wider range of conditions is needed to determine its true potential to transition into practical clinical use.Diabetes research and clinical practice 03/2012; 97(2):195-205. · 2.16 Impact Factor