Search results for "proinflammatory cytokine"
showing 10 items of 454 documents
Pancreatic T cell protein-tyrosine phosphatase deficiency ameliorates cerulein-induced acute pancreatitis.
2014
Background Acute pancreatitis (AP) is a common clinical problem whose incidence has been progressively increasing in recent years. Onset of the disease is trigged by intra-acinar cell activation of digestive enzyme zymogens that induce autodigestion, release of pro-inflammatory cytokines and acinar cell injury. T-cell protein tyrosine phosphatase (TCPTP) is implicated in inflammatory signaling but its significance in AP remains unclear. Results In this study we assessed the role of pancreatic TCPTP in cerulein-induced AP. TCPTP expression was increased at the protein and messenger RNA levels in the early phase of AP in mice and rats. To directly determine whether TCPTP may have a causal rol…
Influence of aging on murine neutrophil and macrophage function against Candida albicans.
2008
Previous work by our group showed that aged C57BL/6 mice develop an altered innate and adaptive immune response to Candida albicans and are more susceptible to systemic primary candidiasis. In this work, we used young (2-3 months old) and aged (18-20 months old) C57BL/6 mice to study in vitro the influence of aging on (1) the fungicidal activity of neutrophils and macrophages, (2) the production of cytokines by resident peritoneal macrophages in response to C. albicans, and (3) cell surface Toll-like receptor (TLR) 2 expression on resident peritoneal macrophages. Our results indicate that murine phagocytes have a fungicidal activity well preserved with aging. In vitro production of proinfla…
Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism
2015
The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. AG126 alleviates the clinical symptoms, diminishes encephalitogenic Th17 differentiation, reduces inflammatory CNS infiltration as well as microglia activation and attenuates myelin damage. We show that AG126 directly inhibits Bruton's tyrosine kinase (BTK), a PTK associated with B cell receptor and Toll-like receptor (TLR) signaling. However, BTK …
Mitochondrial Alterations and Enhanced Human Leukocyte/Endothelial Cell Interactions in Type 1 Diabetes
2020
Type 1 diabetes has been associated with oxidative stress. This study evaluates the rates of oxidative stress, mitochondrial function, leukocyte&ndash
Neuronal injury in chronic CNS inflammation.
2010
Introduction Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system which is characterized by inflammatory demyelination and neurodegeneration. Neurological symptoms include sensory disturbances, optic neuritis, limb weakness, ataxia, bladder dysfunction, cognitive deficits and fatigue. Pathophysiology The inflammation process with MS is promoted by several inflammatory cytokines produced by the immune cells themselves and local resident cells like activated microglia. Consecutive damaging pathways involve the transmigration of activated B lymphocytes and plasma cells, which synthesize antibodies against the myelin sheath, boost the immune atta…
NFAT1 deficit and NFAT2 deficit attenuate EAE via different mechanisms
2015
EAE serves as an animal model for multiple sclerosis and is initiated by autoreactive T cells that infiltrate the CNS. Recognition of myelin-associated Ags within the CNS leads to activation of the transcription factor family NFAT. Here, we demonstrate an essential role for NFAT in disease induction, as the combined lack of NFAT1 (NFATc2) and NFAT2 (NFATc1) completely protected mice. Single deficiency of either NFAT1 or NFAT2 ameliorated the course of EAE, and NFAT2 ablation resulted in an obstructed proinflammatory reaction. However, NFAT1 deficit led to an anti-inflammatory response with nonpathogenic Th17 and Th2 cells concurrently secreting IL-17, IL-4, and IL-10. Both IL-4 and IL-10 co…
Antibodies to proteinase 3 mediate expression of vascular cell adhesion molecule-1 (VCAM-1).
1996
SUMMARY VCAM-1 was first identified as an adhesion molecule induced on human endothelial cells (HEC) by inflammatory cytokines such as IL-1, tumour necrosis factor (TNF), and lipopolysaccharide (LPS). The molecule binds to a variety of leucocytes, including B cells, T cells, basophils, eosinophils and monocytes. Vascular expression of VCAM-1 has been associated with a number of disease states, including rheumatoid arthritis and vasculitis. The detection of antineutrophil cytoplasmic antibodies (ANCA), especially to proteinase 3 (PR3), has become important in the diagnosis of Wegener’s granulomatosis (WG) and related vasculitides. Recently we were able to demonstrate a direct effect of anti-…
Cutting Edge: IL-1α Is a Crucial Danger Signal Triggering Acute Myocardial Inflammation during Myocardial Infarction
2016
Abstract Myocardial infarction (MI) induces a sterile inflammatory response that contributes to adverse cardiac remodeling. The initiating mechanisms of this response remain incompletely defined. We found that necrotic cardiomyocytes released a heat-labile proinflammatory signal activating MAPKs and NF-κB in cardiac fibroblasts, with secondary production of cytokines. This response was abolished in Myd88−/− fibroblasts but was unaffected in nlrp3-deficient fibroblasts. Despite MyD88 dependency, the response was TLR independent, as explored in TLR reporter cells, pointing to a contribution of the IL-1 pathway. Indeed, necrotic cardiomyocytes released IL-1α, but not IL-1β, and the immune acti…
Hypoxia induces proinflammatory cytokines production in alpha-1 antitrypsin deficiency patients
2021
Introduction: Alpha-1 antitrypsin deficiency (AATD) is a rare respiratory condition characterized by abnormal inflammation, where neutrophils play a key role. Excessive neutrophil activation leads to an increase in the oxygen (O2) intake, causing local hypoxia and increased tissue-injury capacity. Tissue hypoxia is part of the inflammatory process so neutrophils can function effectively under these conditions. However, the mechanisms by which neutrophils mediate tissue damage under hypoxia remain unclear. The study aimed to determine whether hypoxia modifies the cytokine profile in AATD patients. Methods: Neutrophils from 22 AATD patients (6 MZ; 9 SZ; 7 ZZ) and 7 controls (MM) were exposed …
Complex regional pain syndrome-significant progress in understanding.
2015
Research into complex regional pain syndrome (CRPS) has made significant progress. First, there was the implementation of the official IASP "Budapest" diagnostic criteria. It would be desirable to also define exclusion and outcome criteria that should be reported in studies. The next step was to recognize the complex pathophysiology. After trauma, some inflammation is physiological; in acute CRPS, this inflammation persists for months. There is an abundance of inflammatory and a lack of anti-inflammatory mediators. This proinflammatory network (cytokines and probably also other mediators) sensitizes the peripheral and spinal nociceptive system, it facilitates the release of neuropeptides fr…