Leptin is an adipocyte-derived hormone/cytokine that links nutrition, metabolism, and immune homeostasis. Leptin is capable of modulating several immune responses. However, the effect of leptin on dendritic cells (DCs) has not yet been recognized. Because DCs are instrumental in the development of immune responses, in this study, we evaluated the impact of leptin on DC activation. We demonstrated the presence of leptin receptor in human immature and mature DCs both at mRNA and protein level and its capacity to transduce leptin signaling leading to STAT-3 phosphorylation. We found no consistent modulation of DC surface molecules known to be critical for their APC function in response to leptin. In contrast, we found that leptin induces rearrangement of actin microfilaments, leading to uropod and ruffle formation. At a functional level, leptin up-regulates the IL-1β, IL-6, IL-12, TNF-α, and MIP-1α production. Coincident with this, leptin-treated DCs stimulate stronger heterologous T cell responses. Furthermore, we found that leptin down-regulates IL-10 production by DCs and drives naive T cell polarization toward Th1 phenotype. Finally, we found that leptin partly protects DCs from spontaneous and UVB-induced apoptosis. Consistent with the antiapoptotic effect of leptin, we observed the activation of NF-κB and a parallel up-regulation of bcl-2 and bcl-xL gene expression. These results provide new insights on the immunoregulatory function of leptin demonstrating its ability to improve DC functions and to promote DC survival. This is of relevance considering a potential application of leptin in immunotherapeutic approaches and its possible use as adjuvant in vaccination protocols.

Metabolic syndrome (MS) represents worldwide public health issue characterized by a set of cardiovascular risk factors including obesity, diabetes, dyslipidemia, hypertension, and impaired glucose tolerance. The link between the MS and the associated diseases is represented by oxidative stress (OS) and by the intracellular redox imbalance, both caused by the persistence of chronic inflammatory conditions that characterize MS. The increase in oxidizing species formation in MS has been accepted as a major underlying mechanism for mitochondrial dysfunction, accumulation of protein and lipid oxidation products, and impairment of the antioxidant systems. These oxidative modifications are recognized as relevant OS biomarkers potentially able to (i) clarify the role of reactive oxygen and nitrogen species in the etiology of the MS, (ii) contribute to the diagnosis/evaluation of the disease’s severity, and (iii) evaluate the utility of possible therapeutic strategies based on natural antioxidants. The antioxidant therapies indeed could be able to (i) counteract systemic as well as mitochondrial-derived OS, (ii) enhance the endogenous antioxidant defenses, (iii) alleviate MS symptoms, and (iv) prevent the complications linked to MS-derived cardiovascular diseases. The focus of this review is to summarize the current knowledge about the role of OS in the development of metabolic alterations characterizing MS, with particular regard to the occurrence of OS-correlated biomarkers, as well as to the use of therapeutic strategies based on natural antioxidants.

Experimental and clinical evidence suggest that oxidative stress causes cellular damage, leading to functional alterations of the tissue. Free radicals may thus play an important role in the pathogenesis of a number of human diseases. Among pro-oxidant agents, oxidized LDL lead to the production of cytotoxic reactive species, e.g., lipoperoxides, causing tissue injury and various subsequent pathologies including intestinal diseases. Thus, to analyze the oxidative damage induced by oxidized LDL to intestinal mucosa, we evaluated morphological and functional changes induced in the human colon adenocarcinoma cell line, Caco-2. In addition, we examined the protective effects exerted by tyrosol, 2-(4-hydroxyphenyl)ethanol, the major phenolic compound present in olive oil. Caco-2 cell treatment (24 and/or 48 h) with oxidized LDL (0.2 g/L) resulted in cytostatic and cytotoxic effects characterized by a series of morphological and functional alterations: membrane damage, modifications of cytoskeleton network, microtubular disorganization, loss of cell-cell and cell-substrate contacts, cell detachment and cell death. The oxidized LDL-induced alterations in Caco-2 cells were almost completely prevented by tyrosol which was added 2 h before and present during the treatments. Our results suggest that some biophenols, such as those contained in olive oil, may counteract the reactive oxygen metabolite-mediated cellular damage and related diseases, by improving in vivo antioxidant defenses.

The primary purpose of these practical guidelines related to Kawasaki disease (KD) is to contribute to prompt diagnosis and appropriate treatment on the basis of different specialists’ contributions in the field. A set of 40 recommendations is provided, divided in two parts: the first describes the definition of KD, its epidemiology, etiopathogenetic hints, presentation, clinical course and general management, including treatment of the acute phase, through specific 23 recommendations.Their application is aimed at improving the rate of treatment with intravenous immunoglobulin and the overall potential development of coronary artery abnormalities in KD. Guidelines, however, should not be considered a norm that limits treatment options of pediatricians and practitioners, as treatment modalities other than those recommended may be required as a result of peculiar medical circumstances, patient’s condition, and disease severity or complications.

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