Interleukin 18 in the CNS Alboni, Silvia; Cervia, Davide; Sugama, Shuei ...
Journal of neuroinflammation,
01/2010, Letnik:
7, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Interleukin (IL)-18 is a cytokine isolated as an important modulator of immune responses and subsequently shown to be pleiotropic. IL-18 and its receptors are expressed in the central nervous system ...(CNS) where they participate in neuroinflammatory/neurodegenerative processes but also influence homeostasis and behavior. Work on IL-18 null mice, the localization of the IL-18 receptor complex in neurons and the neuronal expression of decoy isoforms of the receptor subunits are beginning to reveal the complexity and the significance of the IL-18 system in the CNS. This review summarizes current knowledge on the central role of IL-18 in health and disease.
Objectives Propolis is a honeybee product used extensively in traditional medicine for its antioxidant, anti‐inflammatory, immunomodulatory and anticancer effects. Propolis exhibits a broad spectrum ...of biological activities because it is a complex mixture of natural substances. In this review, the antitumour effects of propolis extracts and its constituents (e.g. flavonoids, terpenes and caffeic acid phenethyl ester) are discussed.
Key findings The effect of propolis on experimental carcinogenesis is discussed, as well as its possible mechanisms of action against tumours, involving apoptosis, cell cycle arrest and interference on metabolic pathways. Propolis seems to be efficient against different tumour cells both in vitro and in vivo, which suggests its potential in the development of new anticancer drugs.
Summary Propolis extracts may be important economically and would allow a relatively inexpensive cancer treatment. Preclinical investigations are needed to further elucidate the benefits of propolis and its antitumour properties.
Propolis is one of the most fascinating honey bee (Apis mellifera L.) products. It is a plant derived product that bees produce from resins that they collect from different plant organs and with ...which they mix beeswax. Propolis is a building material and a protective agent in the bee hive. It also plays an important role in honey bee social immunity, and is widely used by humans as an ingredient of nutraceuticals, over-the-counter preparations and cosmetics. Its chemical composition varies by geographic location, climatic zone and local flora. The understanding of the chemical diversity of propolis is very important in propolis research. In this manuscript, we give an overview of the available methods for studying propolis in different aspects: propolis in the bee colony; chemical composition and plant sources of propolis; biological activity of propolis with respect to bees and humans; and approaches for standardization and quality control for the purposes of industrial application.
The cytokines interleukin 13 and 4 share a common heterodimeric receptor and are important modulators of peripheral allergic reactions. Produced primarily by T-helper type 2 lymphocytes, they are ...typically considered as anti-inflammatory cytokines because they can downregulate the synthesis of T-helper type 1 pro-inflammatory cytokines. Their presence and role in the brain is only beginning to be investigated and the data collected so far shows that these molecules can be produced by microglial cells and possibly by neurons. Attention has so far been given to the possible role of these molecules in neurodegeneration. Both neuroprotective or neurotoxic effects have been proposed based on evidence that interleukin 13 and 4 can reduce inflammation by promoting the M2 microglia phenotype and contributing to the death of microglia M1 phenotype, or by potentiating the effects of oxidative stress on neurons during neuro-inflammation. Remarkably, the heterodimeric subunit IL-13Rα1 of their common receptor was recently demonstrated in dopaminergic neurons of the ventral tegmental area and the substantia nigra pars compacta, suggesting the possibility that both cytokines may affect the activity of these neurons regulating reward, mood, and motor coordination. In mice and man, the gene encoding for IL-13Rα1 is expressed on the X chromosome within the PARK12 region of susceptibility to Parkinson's disease (PD). This, together with finding that IL-13Rα1 contributes to loss of dopaminergic neurons during inflammation, indicates the possibility that these cytokines may contribute to the etiology or the progression of PD.
Highlights • The present study investigated the effects of chronic stress on dopaminergic neurodegeneration. • The chronic stress significantly triggered the dopaminergic neuron loss in the ...substantia nigra. • The chronic stress also reduced noradrenergic neuron in the locus coeruleus. • The activated microglia induced by stress exposures is detected in the substantia nigra and locus coeruleus. • Nitrotyrosine as a marker of oxidative stress is also significantly increased in the substantia nigra and locus coeruleus.
Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that ...can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a structurally related control probe and their use, in combination with chemical proteomics and lipidomics, to determine the impact of acute DAGL blockade on brain lipid networks in mice. Within 2 h, DAGL inhibition produced a striking reorganization of bioactive lipids, including elevations in DAGs and reductions in endocannabinoids and eicosanoids. We also found that DAGLα is a short half-life protein, and the inactivation of DAGLs disrupts cannabinoid receptor-dependent synaptic plasticity and impairs neuroinflammatory responses, including lipopolysaccharide-induced anapyrexia. These findings illuminate the highly interconnected and dynamic nature of lipid signaling pathways in the brain and the central role that DAGL enzymes play in regulating this network.
Highlight • Results from interleukin-18 knockout mice suggest that it may curb appetite and promote lipid utilization in healthy adults consuming high-fat diets.
Gender-specific differences in longevity are reported across species and are mediated by mechanisms not entirely understood. In C57Bl/6 mice, commonly used in aging research, males typically outlive ...females. Since in these animals modest but prolonged reduction of core body (Tc) increased life span, we hypothesized that differential Tc may contribute to sex-specific longevity. Here, we compared the circadian profiles of Tc and locomotor activity (LMA) of male and female C57Bl/6 mice. Since Tc and LMA normally change with age, measurements were carried out in young (3 months) as well as in old (24 months) mice. In young females, Tc was influenced by estrous but was overall higher than in males. This difference was larger in old animals after age eliminated the variations associated with estrous. Although temperature homeostasis is regulated centrally by the sexually dimorphic hypothalamic preoptic area, these differences were uniquely dependent on the gonads. In fact, bilateral gonadectomy abolished the effects of estrous and increased resting Tc in males eliminating all sex-specific differences in Tc and LMA. These effects were only partially mimicked by hormonal replacement as Tc was affected by progesterone and to a lesser extent by estrogen but not by testosterone. Thus, gonadal-dependent modulation of Tc may be one of the physiological parameters contributing to gender-specific differences in longevity.
Mammals maintain a nearly constant core body temperature (Tb) by balancing heat production and heat dissipation. This comes at a high metabolic cost that is sustainable if adequate calorie intake is ...maintained. When nutrients are scarce or experimentally reduced such as during calorie restriction (CR), endotherms can reduce energy expenditure by lowering Tb 1–6. This adaptive response conserves energy, limiting the loss of body weight due to low calorie intake 7–10. Here we show that this response is regulated by the kappa opioid receptor (KOR). CR is associated with increased hypothalamic levels of the endogenous opioid Leu-enkephalin, which is derived from the KOR agonist precursor dynorphin 11. Pharmacological inhibition of KOR, but not of the delta or the mu opioid receptor subtypes, fully blocked CR-induced hypothermia and increased weight loss during CR independent of calorie intake. Similar results were seen with DIO mice subjected to CR. In contrast, inhibiting KOR did not change Tb in animals fed ad libitum (AL). Chemogenetic inhibition of KOR neurons in the hypothalamic preoptic area reduced the CR-induced hypothermia, whereas chemogenetic activation of prodynorphin-expressing neurons in the arcuate or the parabrachial nucleus lowered Tb. These data indicate that KOR signaling is a pivotal regulator of energy homeostasis and can affect body weight during dieting by modulating Tb and energy expenditure.
Display omitted
•Calorie restriction (CR) causes hypothermia and elevates Leu-enkephalin•Activation of prodynorphin neurons lowers temperature•Inhibition of kappa opioid receptor (KOR) neurons reduces CR-induced hypothermia•Blocking KOR halts CR-induced hypothermia, promoting weight loss during dieting
During calorie restriction, endotherms lower core body temperature to limit energy expenditure and weight loss. Cintron-Colon et al. show in mice that this response is regulated centrally by prodynorphin and by kappa opioid receptor (KOR) neurons and that pharmacological inhibition of KOR during dieting prevents hypothermia, increasing weight loss.
PDF
