The detection of pathogen- or danger-associated molecular patterns during an inflammatory injury triggers the activation of cytosolic sensors known as inflammasomes. Once stimulated, these protein complexes can connect to the adaptor protein ASC, which in turn recruits the effector enzyme caspase-1, forming a polymeric structure known as ASC speck. This protein scaffold is responsible for processing cytokines of the IL-1 family into their active forms and evoking the cleavage of gasdermin D, ultimately leading to cell death by pyroptosis.
View Article and Find Full Text PDFThe inflammasomes control the bioactivity of pro-inflammatory cytokines of the interleukin (IL)-1 family. The inflammasome assembled by NLRP3 has been predominantly studied in homogeneous cell populations in vitro, neglecting the influence of cellular interactions that occur in vivo. Here, we show that platelets boost the inflammasome capacity of human macrophages and neutrophils and are critical for IL-1 production by monocytes.
View Article and Find Full Text PDFJoint pain is a distressing symptom of arthritis, and it is frequently persistent even after treatments which reduce local inflammation. Continuous production of algogenic factors activate/sensitize nociceptors in the joint structures and contribute to persistent pain, a challenging and difficult condition to treat. TNF is a crucial cytokine for the pathogenesis of several rheumatic diseases, and its inhibition is a mainstay of treatment to control joint symptoms, including pain.
View Article and Find Full Text PDFThe role of platelets has been extensively studied in the context of coagulation and vascular integrity. Their hemostatic imbalance can lead to known conditions as atherosclerotic plaques, thrombosis, and ischemia. Nevertheless, the knowledge regarding the regulation of different cell types by platelets has been growing exponentially in the past years.
View Article and Find Full Text PDFInfection with the Zika virus (ZIKV) usually causes a mild acute illness, but two major severe syndromes have been described during the epidemic in Brazil: microcephaly and the Guillain-Barré Syndrome. There is now much evidence to show that ZIKV can infect and damage neuronal cells in vitro. In experimental animals, ZIKV has significant neurotropism and can cause brain damage.
View Article and Find Full Text PDFLeukotrienes (LTs) produced from arachidonic acid by the action of 5-lipoxygenase (5-LO) are classical mediators of inflammatory responses. However, studies published in the literature regarding these mediators are contradictory and it remains uncertain whether these lipid mediators play a role in host defense against the fungal pathogen Paracoccidioides brasiliensis. To determine the involvement of LTs in the host response to pulmonary infection, wild-type and LT-deficient mice by targeted disruption of the 5-lipoxygenase gene (knockout mice) were studied following intratracheal challenge with P.
View Article and Find Full Text PDFLeishmania infantum (syn. Leishmania chagasi) is the etiological agent of visceral leishmaniasis (VL) in Brazil. The epidemiology of VL is poorly understood.
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