Browsing by Subject "Piroptosis"

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    Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia: a double-edged sword
    (Wolters Kluwer, Medknow Publications, 2024-04-13) Norte-Muñoz, M.; Portela-Lomba, M.; Sobrado-Calvo, P; Simón, D.; Di Pierdomenico, J.; Gallego-Ortega, A.; Pérez, M.; Cabrera-Maqueda, J.M.; Sierra, J.; Vidal-Sanz, M.; Moreno-Flores, M.T.; Agudo-Barriuso, M; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
    Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system, including retinal ganglion cell axonal growth through the injured optic nerve. Still, it is unknown whether olfactory ensheathing glia also have neuroprotective properties. Olfactory ensheathing glia express brain-derived neurotrophic factor, one of the best neuroprotectants for axotomized retinal ganglion cells. Therefore, we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush. Olfactory ensheathing glia cells from an established rat immortalized clonal cell line, TEG3, were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments. Anatomical and gene expression analyses were performed. Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex class II molecules. Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days, forming an epimembrane. In axotomized retinas, only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days. In these retinas, microglial anatomical activation was higher than after optic nerve crush alone. In intact retinas, both transplants activated microglial cells and caused retinal ganglion cell death at 21 days, a loss that was higher after allotransplantation, triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression. However, neuroprotection of axotomized retinal ganglion cells did not improve with these treatments. The different neuroprotective properties, different toxic effects, and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.
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    The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response
    (Nature, 2014) Baroja-Mazo, Alberto; Gomez, Ana I.; Amores-Iniesta, Joaquín; Compan, Vincent; Barberá-Cremades, María; Yagüe, Jordi; Ruiz-Ortiz, Estibaliz; Antón, Jordi; Buján, Segundo; Couillin, Isabelle; Brough, David; Arostegui, Juan I.; Martínez Cáceres, Carlos Manuel; Martín Sánchez, María Rosario Fátima; Pelegrín Vivancos, Pablo; Bioquímica y Biología Molecular B e Inmunología
    NLRP3 inflammasome assembly activates caspase-1 and mediates the processing and release of the leaderless cytokine IL-1β, and thereby plays a central role in the inflammatory response and in diverse human diseases. Here we report that upon caspase-1 activation oligomerized NLRP3-inflammasome particles are released from macrophages. Recombinant oligomeric protein particles composed of the adapter protein ASC or the cryopyrin-associated periodic syndromes (CAPS) mutant NLRP3 p.D303N, stimulate further caspase-1 activation extracellularly, and also intracellularly upon phagocytosis by surrounding macrophages. ASC oligomeric particles were found in the serum of patients with active CAPS, but not in patients with other inherited autoinflammatory diseases. Our findings support a model whereby the NLRP3-inflammasome, acting as an extracellular oligomeric complex, amplifies the inflammatory response.