17,029 research outputs found
Il ruolo delle HDL nel controllo dell'infiammazione sinoviale
No full textRecent 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
How Factors Involved in the Resolution of Crystal-Induced Inflammation Target IL-1β
No full textOne 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
The translational value of calcium pyrophosphate deposition disease experimental mouse models
No full textThe 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
Gout as autoinflammatory disease: new mechanisms for more appropriated treatment targets.
No full textGout is probably one of the oldest diseases affecting men. This is not surprising especially for the active role that innate immunity seems to play in its pathogenesis. It is fascinating to observe as this ancestral mechanism of defense feels that microcrystals are a danger, quite similar to infectious agents. New advances have revealed that at the base of the powerful inflammatory reaction stimulated by monosodium urate crystals there are many complexes cellular mechanisms, mainly involving inflammasome and toll-like receptors. Subsequently, there is an early increase of proinflammatory cytokines responsible for the acute attack, followed in few days by their reduction along with an increase of anti-inflammatory cytokines, probably main actors of the resolution phase. New targets have also been identified for the reduction of hyperuricemia, the prerequisite of gout, in order to prevent new attacks and the deposition of urate crystals in and around the joints. All these aspects, leading to deeper insight, have suggested new treatments, some of which are already available while others are likely to become available in the near future
Metabolism of crystals within the joint
No full textMonosodium urate (MSU), calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystals deposit in joints and surrounding tissues causing acute inflammation and chronic cartilage damage. A number of endogenous substances and physicochemical conditions affect their precipitation, growth and even dissolution, regulating their metabolism and inflammatory activity. We review how MSU and calcium crystals form within the joints and the various factor which regulate their formation
Immunological Events, Emerging Pharmaceutical Treatments and Therapeutic Potential of Balneotherapy on Osteoarthritis
No full textThe Potential Role of Spa Therapy in Managing Frailty in Rheumatic Patients: A Scoping Review
No full textFrailty is not limited to the elderly, as patients with rheumatic diseases can also experience this condition. The present scoping review aimed to investigate the possibility of using the health resort setting as an alternative location for managing rheumatic patients with frailty. The research resulted in finding several in vitro, in vivo, and clinical studies, resulting in evidence supporting the effectiveness of spa treatments in reducing pain, improving function, and managing comorbidity in rheumatic diseases. Additionally, spa treatments were demonstrated to modulate the MAPK/ERK pathway and the NF-kB pathway's activation and to reduce proinflammatory molecules' secretion in rheumatic diseases, thus suggesting their potential effective role in the regulation of inflammaging in frailty. Moreover, the health resort setting may offer potential resources to reduce risk factors, such as drug consumption, inactivity, and disease severity, and may serve as a setting for developing prevention protocols for frailty. Future research should explore innovative approaches, such as exercise training and early diagnostics, for the overall management of frailty in rheumatic patients in the spa setting
An Article About Albertus C. Van Raalte, Author Unknown, Except for Parts Taken from an Article by Anna C. Post
No full textAn article about Albertus C. Van Raalte, author unknown, except for parts taken from an article by Anna C. Post. The author knew first generation persons in the Holland settlement and therefore, the article has some value.https://digitalcommons.hope.edu/vrp_1890s/1012/thumbnail.jp
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