17 research outputs found
Particulate Matter-Induced Lung Inflammation Increases Systemic Levels of PAI-1 and Activates Coagulation Through Distinct Mechanisms
Exposure of human populations to ambient particulate matter (PM) air pollution significantly contributes to the mortality attributable to ischemic cardiovascular events. We reported that mice treated with intratracheally instilled PM develop a prothrombotic state that requires the release of IL-6 by alveolar macrophages. We sought to determine whether exposure of mice to PM increases the levels of PAI-1, a major regulator of thrombolysis, via a similar or distinct mechanism. mice but was absent in mice treated with etanercept, a TNF-α inhibitor. Treatment with etanercept did not prevent the PM-induced tendency toward thrombus formation.Mice exposed to inhaled PM exhibited a TNF-α-dependent increase in PAI-1 and an IL-6-dependent activation of coagulation. These results suggest that multiple mechanisms link PM-induced lung inflammation with the development of a prothrombotic state
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field
Nonrandom Distribution of the One-Disulfide Intermediates in the Regeneration of Ribonuclease A â
Kinetic Studies of the Regeneration of Recombinant Hirudin Variant 1 with Oxidized and Reduced Dithiothreitol â
Circular Dichroism Evidence for the Presence of Burst-Phase Intermediates on the Conformational Folding Pathway of Ribonuclease A â
Kinetic and Thermodynamic Studies of the Folding/Unfolding of a Tryptophan-Containing Mutant of Ribonuclease A â
Retention of the Cis Proline Conformation in Tripeptide Fragments of Bovine Pancreatic Ribonuclease A Containing a Non-natural Proline Analogue, 5,5-Dimethylproline
The IÎșB Kinase Complex (IKK) Contains Two Kinase Subunits, IKKα and IKKÎČ, Necessary for IÎșB Phosphorylation and NF-ÎșB Activation
Requirement for NF-ÎșB signalling in a mouse model of lung adenocarcinoma
NF-ÎșB transcription factors function as crucial regulators of inflammatory and immune responses as well as of cell survival. They have also been implicated in cellular transformation and tumorigenesis. However, despite extensive biochemical characterization of NF-ÎșB signalling during the past twenty years, the requirement for NF-ÎșB in tumour development in vivo, particularly in solid tumours, is not completely understood. Here we show that the NF-ÎșB pathway is required for the development of tumours in a mouse model of lung adenocarcinoma. Concomitant loss of p53 (also known as Trp53) and expression of oncogenic Kras(G12D) resulted in NF-ÎșB activation in primary mouse embryonic fibroblasts. Conversely, in lung tumour cell lines expressing Kras(G12D) and lacking p53, p53 restoration led to NF-ÎșB inhibition. Furthermore, the inhibition of NF-ÎșB signalling induced apoptosis in p53-null lung cancer cell lines. Inhibition of the pathway in lung tumours in vivo, from the time of tumour initiation or after tumour progression, resulted in significantly reduced tumour development. Together, these results indicate a critical function for NF-ÎșB signalling in lung tumour development and, further, that this requirement depends on p53 status. These findings also provide support for the development of NF-ÎșB inhibitory drugs as targeted therapies for the treatment of patients with defined mutations in Kras and p53.Howard Hughes Medical InstituteNational Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051)Leukemia & Lymphoma Society of America (Fellowship Award