1,721,100 research outputs found
Il ruolo delle HDL nel controllo dell'infiammazione sinoviale
Full text linkRecent reports suggest that apolipoproteins (apo) exert an important role in controlling inflammation. It has been demonstrated that high density lipoprotein (HDL) are able to block the contact-mediated activation of monocytes-macrophages by stimulated T lymphocytes and inhibit the production of IL-1ß and TNF?.
Aim of the thesis: To investigate the effects of HDL on MCP-1 release from monosodium urate crystals-stimulated synoviocytes and IL-1ß, TNF? and IL-1Ra release from microparticles-stimulated monocytes.
Methods: Human synoviocytes were obtained by synovial tissue explants from patients with osteoarthritis and stimulated with monosodium urate (MSU) crystals (0.01-0.25 mg/ml) in the presence or absence of human HDL (50 e 100 ?g/ml).
Microparticles (MP) were isolated by ultracentrifugation from T lymphocytes and HUT-78 cultures stimulated with phorbol myristate acetate (PMA) (5 ng/ml) and phytohemagglutinin (PHA) (1 ?g/ml) for 48 and 6 h respectively. The cellular origin of MP was determined by flow cytometry. Human monocytes were activated for 48 h by MP from T lymphocytes at concentrations of 13.3 ?g/ml and 26.6 ?g/ml. HUT-78-derived MP were used at a concentration of 1.5-6 ?g/ml in the presence or absence of human HDL (0.2 mg/ml).
HDL were isolated from peripheral blood of healthy volunteers by ultracentrifugation.
MCP-1 was determined in cultured cells by western blotting and confocal microscopy, while the production of IL-1ß, TNF? and IL-1Ra was measured in culture supernatants by ELISA.
Results: Confocal microscopy and western blotting analysis revealed that MCP-1 resides in small cytoplasmatic granules on non stimulated cells. The exposure of synoviocytes to MSU crystals leads to a decrease of intracellular levels of the protein and an increase of extracellular chemokine concentration. The treatment of synoviocytes with HDL causes a dose-dependent inhibition of the release of MCP-1 which maintains its storage in granules. The same effect was observed pre-incubating cells with HDL 1 h before crystal activation.
MP generated by stimulated T cells induce a production of IL-1ß, TNF? and IL-1Ra in monocyte cultures higher than those obtained by MP from unstimulated T lymphocytes. It has also been observed that monocytes stimulated with MP generated by activated HUT-78 release IL-1ß, TNF? and IL-1Ra in a dose-dependent manner. The treatment with HDL inhibits IL-1ß and TNF? levels, whereas the production of IL-1Ra remains unchanged.
Conclusion: The inhibitory activity of HDL highlighted by the pre-treatment of cells is probably due to a direct action of lipoproteins on synoviocytes rather than to their adsorption on the surface of the crystals. By inhibiting MCP-1 release, HDL may limit the inflammatory process.
The production of cytokines depends on the activation level of cells from which MP take origin.
The almost complete inhibition of IL-1ß and TNF? levels by HDL lead us to hypothesize that HDL control cellular contact between MP and monocytes, as already observed in the lymphocytes T - monocytes interaction
The translational value of calcium pyrophosphate deposition disease experimental mouse models
Full text linkThe deposition of calcium pyrophosphate (CPP) crystals in joint tissues causes acute and chronic arthritis that commonly affect the adult and elderly population. Experimental calcium pyrophosphate deposition disease (CPPD) models are divided into genetically modified models and crystal-induced inflammation models. The former do not reproduce phenotypes overlapping with the human disease, while in the latter, the direct injection of crystals into the ankles, dorsal air pouch or peritoneum constitutes a useful and reliable methodology that resembles the CPP induced-inflammatory condition in humans. The translational importance of the induced model is also strengthened by the fact that the key molecular and cellular mediators involved in inflammation are shared between humans and laboratory rodents. Although, in vivo models are indispensable tools for studying the pathogenesis of the CPPD and testing new therapies, their development is still at an early stage and major efforts are needed to address this issue. Here, we analyze the strenghts and limitations of each currently available CPPD in vivo model, and critically discuss their translational value
Rôle du complément dans la pathogénie de l’arthrose
No full text»» Des études récentes démontrent que l’inflammation articulaire joue un rôle important dans l’arthrose, agissant aussi bien sur le déclenchement que sur les symptômes et la progression de la maladie.
»» La réponse inflammatoire dans l’arthrose semble être induite par l’activation de la voie de signalisation de l’immunité innée.
»» L’activation du système du complément joue un rôle clé dans la pathogénie de l’arthrose.
»» Une augmentation de l’expression et de l’activation du complément a été observée dans le liquide synovial et dans les membranes synoviales de patients atteints d’arthrose par rapport aux sujets témoins normaux
How Factors Involved in the Resolution of Crystal-Induced Inflammation Target IL-1β
Full text linkOne of the main clinical features characterizing crystal-induced inflammation is its spontaneous resolution. The aim of this review is to outline the various factors involved in the self-limiting course of crystal-induced inflammation focusing on their effect on IL-1β production. Endogenous molecules that are induced or locally recruited by the process itself, inhibitory proteins naturally present in the joint and exogenous dietary factors are discussed. Aside from the classical well-known molecules involved in the resolution of crystal-induced acute attack such as TGFβ, IL-10, IL-1Ra, and lipoproteins, particular attention is paid to recently uncovered mechanisms such as the aggregation of neutrophil extracellular traps, the release of ectosomes from neutrophil surface, and alpha-1-anti-trypsin-mediated IL-1 inhibition
NK cells isolated from synovial fluid amplify the inflammatory response of fibroblast-like synoviocytes
No full textOne year in review 2018: gout
No full textGout is the most common form of inflammatory arthropathy, and is associated with excruciating pain, major impairment of quality of life, and increased risk of comorbidities and mortality. Although gout has somehow been neglected by researchers and clinicians in the past, in more recent times there has been a renewed interest in this disease, which has led to major improvements in its management. This article reviews the new clinical and experimental evidence about gout that emerged in 2017 and in the first half of 2018
- …
