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Ferritin heavy chain supports stability and function of the regulatory T cell l...

Wu, Qian; Carlos, Ana Rita; Braza, Faouzi; Bergman, Marie-Louise; Kitoko, Jamil Z; Bastos-Amador, Patricia; Cuadrado, Eloy; Martins, Rui

Regulatory T (TREG) cells develop via a program orchestrated by the transcription factor forkhead box protein P3 (FOXP3). Maintenance of the TREG cell lineage relies on sustained FOXP3 transcription via a mechanism involving demethylation of cytosine-phosphate-guanine (CpG)-rich elements at conserved non-coding sequences (CNS) in the FOXP3 locus. This cytosine demethylation is catalyzed by the ten–eleven transl...


DNA damage independent inhibition of NF-κB transcription by anthracyclines

Pedroso, Dora; Chora, Ângelo Ferreira; Kyriakou, Eleni; Pejanovic, Nadja; Colaço, Henrique; Gozzelino, Raffaella; Barros, André; Willmann, Katharina

Anthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning and to eviction of histones from select sites in the genome. Here, we show that the extensively used anthracyclines Doxorubicin, Daunorubicin, and Epirubicin decrease the transcription of nuclear factor kappa B (NF-κB)-dependent gene targ...


Azithromycin does not improve disease severity in acute experimental pancreatitis

Weis, Sebastian; Heindl, Mario; Carvalho, Tânia; Jentho, Elisa; Lorenz, Jana; Sommerer, Ines; Mössner, Joachim; Hoffmeister, Albrecht

Acute pancreatitis is a severe systemic disease triggered by a sterile inflammation and initial local tissue damage of the pancreas. Immune cells infiltrating into the pancreas are main mediators of acute pancreatitis pathogenesis. In addition to their antimicrobial potency, macrolides possess anti-inflammatory and immunomodulatory properties which are routinely used in patients with chronic airway infections a...


Tissue damage control in disease tolerance

Soares, Miguel P; Gozzelino, Raffaella; Weis, Sebastian

Immune-driven resistance mechanisms are the prevailing host defense strategy against infection. By contrast, disease tolerance mechanisms limit disease severity by preventing tissue damage or ameliorating tissue function without interfering with pathogen load. We propose here that tissue damage control underlies many of the protective effects of disease tolerance. We explore the mechanisms of cellular adaptatio...


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