The clear association of Th17 cells with autoimmune pathogenicity implicates cytokines as critical mediators chronic diseases such EAE. To study the impact IL-17A on CNS inflammation, we generated transgenic mice in which high levels expression could be initiated after Cre-mediated recombination. Although ubiquitous overexpression led to skin inflammation and granulocytosis, T cell-specific did not have a perceptible development health mice. In context EAE, neither cell-driven nor its...

Reactive astrocytes are implicated in the development and maintenance of neuroinflammation demyelinating disease multiple sclerosis (MS). The sphingosine kinase 1 (SphK1)/sphingosine1-phosphate (S1P) receptor signaling pathway is involved modulation inflammatory response many cell types, but role S1P subtype 3 (S1P(3)) SphK1 activated rat has not been defined.Using immunohistochemistry we observed upregulation S1P(3) expression on reactive macrophages MS lesions. Increased mRNA protein...

Interferon gamma (IFN-γ) has been shown to be produced within multiple sclerosis (MS) lesions by infiltrating lymphocytes; systemic administration of this cytokine induces exacerbation the disease. The aim current study was establish contribution IFN-γ oligodendrocyte (OL) injury. Our studies utilized cultured human OLs, obtained dissociation surgically derived non-MS adult brain tissue. Neither cell survival nor myelin basic protein (MBP) gene expression were affected after 96 hours...

Smoking cessation reduces the risk of developing smoking-related diseases. Although smoking prevalence has declined, many continue cigarettes. Switching completely to smoke-free alternatives like Tobacco Heating System (THS) 2.2-a heated tobacco product for which there is evidence demonstrating significantly reduced formation and exposure harmful chemicals compared cigarettes-has potential reduce harm caused by continuing smoke

Background Growing evidence indicates that noncombustible products could be a tobacco harm reduction tool for smokers who do not quit. The Tobacco Heating System (THS) emits substantially lower levels of harmful cigarette smoke constituents, and previous randomized clinical studies showed improved biomarkers potential (BoPH) linked to smoking-related disease.

The kinin B1 receptor is an inducible expressed in response to inflammatory mediators. We sought determine whether can be on human brain endothelial cells (HBECs) vitro and signaling via this regulate permeability chemokine production properties of these cells. Multiplex RT-PCR amplification western blot techniques were used evaluate expression by HBECs. Although mRNA protein could not detected resting HBECs, interferon-γ induced a dose- time-dependent up-regulation Stimulation...

Oligodendrocytes generate and maintain myelin, which is essential for axonal function protection of the mammalian central nervous system. To advance our molecular understanding differentiation by these cells, we screened libraries pharmacologically active compounds identified inducers Oli-neu, a stable cell line mouse oligodendrocyte precursors (OPCs). We four broad classes inducers, namely, forskolin/cAMP (protein kinase A activators), steroids (glucocorticoids retinoic acid), ErbB2...

We have generated transgenic mice that harbor humanized type I interferon receptors (IFNARs) enabling the study of human interferons (Hu-IFN-Is) in mice. These "HyBNAR" (Hybrid IFNAR) encode variants IFNAR1 and IFNAR2 with extracellular domains being fused to transmembrane cytoplasmic segments mouse sequence. B16F1 melanoma cells harboring HyBNAR construct specifically bound Hu-IFN-Is were rendered sensitive Hu-IFN-I stimulated anti-proliferation, STAT1 activation a prototypical IFN-I...

Smoking increases lipid levels, including triglycerides, leading to increased cardiovascular disease risk. We performed a meta-analysis quantify the effects of smoking and cessation on triglyceride levels. The PubMed Scopus databases were searched identify studies reporting either levels in smokers non-smokers or Fixed- random-effects models used perform analyses when three more studies/comparisons available. identified 169 21 evaluating cessation, respectively, Triglyceride 0.50 mmol/L (95%...

The expression of NG2 chondroitin sulfate has been widely associated with oligodendrocyte precursors in rodents. We used a monoclonal antibody (9.2.27) against the human homologue rat to determine whether this molecule was specific glial cell population present dissociated preparations derived from adult and fetal brain tissue. Our data, using FACS immunocytochemical analyses immediately ex vivo or cultured cells, indicate that large majority expressing cells belonged microglial lineage...

Multiple sclerosis (MS) is a neuroinflammatory disease characterized by progressive loss of myelin and failure oligodendrocyte (OL)-mediated remyelination, particularly in the phases disease. An improved understanding signaling mechanisms that control differentiation OL precursors may lead to identification new therapeutic targets for remyelination MS. About 100 mammalian Protein Tyrosine Phosphatases (PTPs) are known, many which involved both health We have undertaken systematic genomic...

We have previously reported that neonatal rat oligodendrocytes (OLGs) express and secrete neuregulins (NRGs) (Raabe et al., 1997). This laboratory has also shown NRGs stimulate the differentiation of OLGs these cells erbB receptors for In this study, we characterized NRG expression in adult human OLG cultures isolated from temporal lobe resection intractable epilepsy patients. Using immunocytochemistry Western blotting, find contain both α β isoforms NRGs. addition, blots show as...

Protein tyrosine phosphatase receptor type Z (Ptprz) is widely expressed in the mammalian central nervous system and has been suggested to regulate oligodendrocyte survival differentiation. We investigated role of Ptprz remyelination after acute, toxin-induced demyelination null mice. found neither obvious impairment recruitment precursor cells, astrocytes, or reactive microglia/macrophage lesions nor a failure for cells differentiate remyelinate axons at lesions. However, we observed an...

Cigarette smoking induces cytochrome P450 1A2 (CYP1A2) expression and activity, while cessation normalizes the levels of this enzyme. The aim publication is to summarize data on CYP1A2 gene activity in preclinical clinical studies Tobacco Heating System (THS), currently marketed as IQOS® with HEETs®, potential effects be expected upon switching reduced-risk products (RRPs).We summarized PMI's from cigarette THS.Data four mouse rat showed that, either smoke exposure or THS exposure,...

Background Smoking is a significant risk factor for periodontal disease and tooth loss, as shown in several clinical studies comparing smokers nonsmokers. Although only few longitudinal have assessed the outcome of after smoking cessation, they indicated that recovery nonsurgical treatment was more successful those who had quit smoking. As part tobacco harm reduction strategies, substituting cigarettes with alternative, less harmful products an approach complementary to cessation would...

To evaluate the reduced-risk potential of alternative tobacco products, biomarkers that are involved in biological pathways affected by cigarette smoking and cessation needed. Isoprostanes, a measure oxidative stress, appear to be influenced reversible upon therefore could good biomarker. This review aims at quantifying effect on levels urinary 8-iso prostaglandin F2α (8-epi-PGF2α), an isoprostane.PubMed Scopus databases were searched for publications reported 8-epi-PGF2α smokers nonsmokers...

The plasticity of mature oligodendrocytes was studied in aggregating brain cell cultures at the period maximal expression myelin marker proteins. protein kinase C (PKC)-activating tumor promoters mezerein and phorbol 12-myristate 13-acetate (PMA), but not inactive ester analog 4α-PMA, caused a pronounced decrease basic (MBP) content 2′,3′-cyclic nucleotide 3′-phosphohydrolase (CNP) activity. In contrast, myelin/oligodendrocyte (MOG) affected relatively little. Northern blot analyses showed...

Apolipoproteins are major components of lipoproteins such as high-density lipoprotein (HDL) and very-low-density considered nontraditional markers in the risk assessment for cardiovascular disease. The goal this review was to quantify effects smoking cessation on serum levels apolipoproteins AI, AII, B ratio AI.PubMed Scopus were searched up June 2021 identify publications that reported apolipoprotein B/AI smokers nonsmokers well articles reporting effect same endpoints. Meta-analyses...