Recursos de colección

ARCA - Access to Research and Communication Annals - IGC Repository (819 recursos)

The Institutional Repository of Instituto Gulbenkian de Ciência, developed under the project RCAAP, is intended to collect, preserve and promote open access to the intellectual production of their researchers.

Innate Immunity and Inflammation

Mostrando recursos 1 - 7 de 7

  1. Effect of celastrol on bone structure and mechanics in arthritic rats

    Cascão, Rita; Vidal, Bruno; Jalmari Finnilä, Mikko Arttu; Lopes, Inês Pascoal; Teixeira, Rui Lourenço; Saarakkala, Simo; Moita, Luis Ferreira; Fonseca, João Eurico
    Rheumatoid arthritis (RA) is characterised by chronic inflammation leading to articular bone and cartilage damage. Despite recent progress in RA management, adverse effects, lack of efficacy and economic barriers to treatment access still limit therapeutic success. Therefore, safer and less expensive treatments that control inflammation and bone resorption are needed. We have previously shown that celastrol is a candidate for RA treatment. We have observed that it inhibits both interleukin (IL)-1β and tumor necrosis factor (TNF) in vitro, and that it has anti-inflammatory properties and ability to decrease synovial CD68+ macrophages in vivo. Herein our goal was to evaluate the...

  2. Effect of celastrol on bone structure and mechanics in arthritic rats

    Cascão, Rita; Vidal, Bruno; Jalmari Finnilä, Mikko Arttu; Lopes, Inês Pascoal; Teixeira, Rui Lourenço; Saarakkala, Simo; Moita, Luis Ferreira; Fonseca, João Eurico
    Rheumatoid arthritis (RA) is characterised by chronic inflammation leading to articular bone and cartilage damage. Despite recent progress in RA management, adverse effects, lack of efficacy and economic barriers to treatment access still limit therapeutic success. Therefore, safer and less expensive treatments that control inflammation and bone resorption are needed. We have previously shown that celastrol is a candidate for RA treatment. We have observed that it inhibits both interleukin (IL)-1β and tumor necrosis factor (TNF) in vitro, and that it has anti-inflammatory properties and ability to decrease synovial CD68+ macrophages in vivo. Herein our goal was to evaluate the...

  3. Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

    Cascão, Rita; Fonseca, João E.; Moita, Luis F.
    This deposit is composed by the main article, and it hasn't any supplementary materials associated.

  4. Highly dynamic host actin reorganization around developing Plasmodium inside hepatocytes

    Gomes-Santos, Carina S S; Itoe, Maurice A; Afonso, Cristina; Henriques, Ricardo; Gardner, Rui; Sepúlveda, Nuno; Simões, Pedro D; Raquel, Helena; Almeida, António Paulo; Moita, Luis F; Frischknecht, Friedrich; Mota, Maria M
    Plasmodium sporozoites are transmitted by Anopheles mosquitoes and infect hepatocytes, where a single sporozoite replicates into thousands of merozoites inside a parasitophorous vacuole. The nature of the Plasmodium-host cell interface, as well as the interactions occurring between these two organisms, remains largely unknown. Here we show that highly dynamic hepatocyte actin reorganization events occur around developing Plasmodium berghei parasites inside human hepatoma cells. Actin reorganization is most prominent between 10 to 16 hours post infection and depends on the actin severing and capping protein, gelsolin. Live cell imaging studies also suggest that the hepatocyte cytoskeleton may contribute to parasite elimination...

  5. shRNA-Based Screen Identifies Endocytic Recycling Pathway Components That Act as Genetic Modifiers of Alpha-Synuclein Aggregation, Secretion and Toxicity

    Gonçalves, Susana A; Macedo, Diana; Raquel, Helena; Simões, Pedro D; Giorgini, Flaviano; Ramalho, José S; Barral, Duarte C; Ferreira Moita, Luís; Outeiro, Tiago Fleming
    Alpha-Synuclein (aSyn) misfolding and aggregation is common in several neurodegenerative diseases, including Parkinson's disease and dementia with Lewy bodies, which are known as synucleinopathies. Accumulating evidence suggests that secretion and cell-to-cell trafficking of pathological forms of aSyn may explain the typical patterns of disease progression. However, the molecular mechanisms controlling aSyn aggregation and spreading of pathology are still elusive. In order to obtain unbiased information about the molecular regulators of aSyn oligomerization, we performed a microscopy-based large-scale RNAi screen in living cells. Interestingly, we identified nine Rab GTPase and kinase genes that modulated aSyn aggregation, toxicity and levels. From those,...

  6. Endosomal MR1 Trafficking Plays a Key Role in Presentation of Mycobacterium tuberculosis Ligands to MAIT Cells

    Harriff, Melanie J.; Karamooz, Elham; Burr, Ansen; Grant, Wilmon F.; Canfield, Elizabeth T.; Sorensen, Michelle L.; Moita, Luis F.; Lewinsohn, David M.
    Mucosal-Associated Invariant T (MAIT) cells, present in high frequency in airway and other mucosal tissues, have Th1 effector capacity positioning them to play a critical role in the early immune response to intracellular pathogens, including Mycobacterium tuberculosis (Mtb). MR1 is a highly conserved Class I-like molecule that presents vitamin B metabolites to MAIT cells. The mechanisms for loading these ubiquitous small molecules are likely to be tightly regulated to prevent inappropriate MAIT cell activation. To define the intracellular localization of MR1, we analyzed the distribution of an MR1-GFP fusion protein in antigen presenting cells. We found that MR1 localized to...

  7. Sepsis: the need for tolerance not complacency

    Velho, Tiago R; Santos, Isa; Póvoa, Pedro; Moita, Luis Ferreira
    Sepsis is a life-threatening condition that arises as a systemic inflammatory response syndrome to an infection. Its uncontrolled progression can in frequent cases lead to multiple organ failure, which is still associated with high mortality rates. Modern antibiotics made clear that the infection is only an initiating, and not always necessary, event of this syndrome as many patients with sepsis die despite effective eradication of the inciting pathogen. This observation critically contributed to a paradigm shift that focused the pathogenesis of sepsis on the host and not on the pathogen. However, therapeutic strategies based on the inhibition of proinflammatory critical...

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