inflammation

Could TNF-antagonists be a novel treatment strategy for BPH patients?

Tumor necrosis factor (TNF) is widely recognized as a pivotal player in both systemic and local inflammatory processes. Due to the critical role this molecule has in driving both chronic and acute inflammation, it was among the earliest therapeutic targets utilized for pa-tients with autoimmune (AI) diseases. While inflamma-tion in the prostate is commonly observed, the organ has not previously been considered a target of systemic inflammation associated with some AI diseases. In pa-tients with benign prostatic hyperplasia (BPH), chronic inflammation is common, and immune cells represent a significant proportion of cells in the organ. Accumulation of inflammatory cells may be a response to an initial in-sult and/or a factor in driving BPH pathogenesis. Cer-tainly, inflammation can limit the efficacy of existing medical therapies in these patients. We previously showed that a pattern of gene expression in BPH tissues from patients who had progressed to indication-specific surgery was consistent with the changes seen in AI dis-eases. Recently, we demonstrated that patients with AI disease have an approximately 50% increase in (…)

Cellular mechanisms linking cancers to obesity

Obesity is epidemiologically linked to 13 forms of cancer. The local and systemic obese environment is complex and likely affect tumors through multiple avenues. This includes modulation of cancer cell phenotypes and the composition of the tumor microenvironment. A molecular understanding of how obesity links to cancer holds promise for identifying candidate genes for targeted therapy for obese cancer patient. Herein, we review both the cell-autonomous and non-cell-autonomous mechanisms linking obesity and cancer as well as provide an overview of the mouse model systems applied to study this.

Roles of phosphatidyl inositol 3 kinase gamma (PI3Kγ) in respiratory diseases

Phosphatidyl inositol 3 kinase gamma (PI3Kγ) is expressed in all the cell types that are involved in airway inflammation and disease, including not only leukocytes, but also structural cells, where it is expressed at very low levels under physiological conditions, while is significantly upregulated after stress. In the airways, PI3Kγ behaves as a trigger or a controller, depending on the pathological context. In this review, the contribution of PI3Kγ in a plethora of respiratory diseases, spanning from acute lung injury, pulmonary fibrosis, asthma, cystic fibrosis and response to both bacterial and viral pathogens, will be commented.

TLR4: the fall guy in sepsis?

WHOLE GENOME CRISPR SCREEN AND THE IDENTIFICATION OF Treml4 We reasoned that if immune cells undergo apoptosis during sepsis, ablation of the gene responsible for this in a sub-population should … Read more

Necroptosis, tumor necrosis and tumorigenesis

INTRODUCTION Cell death can happen through either an active, regulated process, known as programmed cell death, or a passive, uncontrolled course. Because of the dramatic morphological differences of these two … Read more

Inflammation induced PD-L1-specific T cells

PD-L1-specific T cells are a natural part of the T-cell repertoire in humans. Hence, we have previously described spontaneous CD8+ and CD4+ T-cell reactivity against PD-L1 in the peripheral blood of patients with various cancers as well as in healthy donors. It is well described that the expression of the PD-L1 protein is introduced in cells by pro-inflammatory cytokines, e.g. IFN-γ. In the current study, we were able to directly link inflammation with PD-L1-specific T cells by showing that inflammatory mediators such as IFN-γ generate measurable numbers of PD-L1-specific T cells in human PBMCs as well as in in vivo models. These PD-L1-specific T cells can vigorously modulate the cell compartments of the local environment. PD-L1-specific T cells may be important for immune homeostasis by sustaining the ongoing inflammatory response by the suppression of regulatory cell function both (…)

Immunometabolic cross-talk in the inflamed heart

Inflammatory processes underlie many diseases associated with injury of the heart muscle, including conditions without an obvious inflammatory pathogenic component such as hypertensive and diabetic cardiomyopathy. Persistence of cardiac inflammation can cause irreversible structural and functional deficits. Some are induced by direct damage of the heart muscle by cellular and soluble mediators but also by metabolic adaptations sustained by the inflammatory microenvironment. It is well established that both cardiomyocytes and immune cells undergo metabolic reprogramming in the site of inflammation, which allow them to deal with decreased availability of nutrients and oxygen. However, like in cancer, competition for nutrients and increased production of signalling metabolites such as lactate initiate a metabolic cross-talk between immune cells and cardiomyocytes which, we propose, might tip the balance between resolution of the inflammation versus adverse cardiac remodeling. Here we review our current understanding of the metabolic reprogramming of both heart tissue and immune (…)