IL-33 stimulates expression of the GPR84 (EX33) fatty acid receptor gene and of cytokine and chemokine genes in human adipocytes

Expression of GPCR fatty acid sensor/receptor genes in adipocytes is modulated by inflammatory mediators, particularly IL-1β. In this study we examined whether the IL-1 gene superfamily member, IL-33, also regulates expression of the fatty acid receptor genes in adipocytes. Human fat cells, differentiated from preadipocytes, were incubated with IL-33 at three different dose levels for 3 or 24 h and mRNA measured by qPCR. Treatment with IL-33 induced a dose-dependent increase in GPR84 mRNA at 3 h, the level with the highest dose being 13.7-fold greater than in controls. Stimulation of GPR84 expression was transitory; the mRNA level was not elevated at 24 h. In contrast to GPR84, IL-33 had no effect on GPR120 expression. IL-33 markedly stimulated expression of the IL1B, CCL2, IL6, CXCL2 and CSF3 genes, but there was no effect on ADIPOQ expression. The largest effect was on CSF3, the mRNA level of which increased 183-fold over controls at 3 h with the highest dose of IL-33; there was a parallel increase in the secretion of G-CSF protein into the medium. It is concluded that in human adipocytes IL-33, which is synthesised in adipose tissue, has a strong stimulatory effect on the expression of cytokine and chemokine genes, particularly CSF3, and on the expression of GPR84, a pro-inflammatory fatty acid receptor

PCR array and protein array studies demonstrate that IL-1β (interleukin-1β) stimulates the expression and secretion of multiple cytokines and chemokines in human adipocytes

The role of IL-1β in regulating the expression and secretion of cytokines and chemokines by human adipocytes was examined. Adipocytes were incubated with human IL-1β for 4 or 24 h. The expression of a panel of 84 cytokine/chemokine genes was probed using PCR arrays. IL-1β stimulated the expression of >30 cytokine/chemokine genes on the arrays; 15 showed >100-fold increases in mRNA at 4 or 24 h including CSF3, CXCL1, CXCL2, CXCL12 and IL8. CSF3 exhibited a 10,000-fold increase in mRNA at 4 h. ADIPOQ was among the genes whose expression was inhibited. Protein arrays were used to examine the secretion of cytokines/chemokines from adipocytes. IL-1β stimulated the secretion of multiple cytokines/chemokines including MCP-1, IL-8, IP-10, MIP-1α and MCP-4. The most responsive was IP-10, which exhibited a 5,000-fold increase in secretion with IL-1β. IL-1β is likely to play a substantial role in stimulating the inflammatory response in human adipocytes in obesity

Correlates of dermis thickness in mouse models with a range of obesity, insulin resistance and diabetic states

Diabetic complications of the skin regarding skin structure have been well documented and researched, notably in relation to wound healing. Recently it has also been discovered that dermis thickness may also be reduced in type 2 diabetic patients. Peripheral damage in diabetes has been attributed to inflammation, as well as hyperglycaemia resulting from insulin resistance. However, this has not been investigated specifically in relation to dermis thickness. This study used mouse models with a range of obesity, insulin resistance and diabetic states to investigate the extent of reduction in dermis thickness that results from these conditions and to elucidate the correlation of dermis thickness with both biomarkers of insulin resistance and whole-body and local proinflammatory cytokine levels, which can both directly damage tissues and be the causative factor of the insulin resistance. The results suggest that the reduced dermis thickness observed in type 2 diabetes is likely a result of hyperglycaemia resulting from insulin resistance rather than the increased proinflammatory milieu resulting from insulin resistance and obesity

PCR arrays indicate that the expression of extracellular matrix and cell adhesion genes in human adipocytes is regulated by IL-1β (interleukin-1β)

The role of IL-1β in regulating the expression of extracellular matrix (ECM) and cell adhesion genes in human adipocytes has been examined. Adipocytes differentiated in culture were incubated with IL-1β for 4 or 24 h and RNA probed with PCR arrays for 84 ECM and cell adhesion genes. Treatment with IL-1β resulted in changes in the expression at one or both time points of ~50% of the genes probed by the arrays, the majority being down-regulated. Genes whose expression was down-regulated by IL-1β included those encoding several collagen chains and integrin subunits. In contrast, IL-1β induced substantial increases (>10-fold) in the expression of ICAM1, VCAM1, MMP1 and MMP3; the secretion of the encoded proteins was also markedly stimulated. IL-1β has a pervasive effect on the expression of ECM and cell adhesion genes in human adipocytes, consistent with the derangement of tissue structure during inflammation in white fat

Preventive effects of Salvia officinalis leaf extract on insulin resistance and inflammation in a model of high fat diet-induced obesity in mice that responds to rosiglitazone

Background Salvia officinalis (sage) is a native plant to the Mediterranean region and has been used for a long time in traditional medicine for various diseases. We investigated possible anti-diabetic, anti-inflammatory and anti-obesity effects of sage methanol (MetOH) extract in a nutritional mouse model of obesity, inflammation and insulin resistance, as well as its effects on lipolysis and lipogenesis in 3T3-L1 cells. Methods Diet-induced obese (DIO) mice were treated for 5 weeks with sage methanol extract (100 and 400 mg.kg-1/day. bid), or rosiglitazone (3 mg.kg-1/day. bid), as a positive control. Energy expenditure, food intake, body weight, fat mass, liver glycogen and lipid content were evaluated. Blood glucose, and plasma levels of insulin, lipids leptin and pro- and anti-inflammatory cytokines were measured throughout the experiment. The effects of sage MetOH extract on lipolysis and lipogenesis were tested in vitro in 3T3-L1 cells. Results After two weeks of treatment, the lower dose of sage MetOH extract decreased blood glucose and plasma insulin levels during an oral glucose tolerance test (OGTT). An insulin tolerance test (ITT), performed at day 29 confirmed that sage improved insulin sensitivity. Groups treated with low dose sage and rosiglitazone showed very similar effects on OGTT and ITT. Sage also improved HOMA-IR, triglycerides and NEFA. Treatment with the low dose increased the plasma levels of the anti-inflammatory cytokines IL-2, IL-4 and IL-10 and reduced the plasma level of the pro-inflammatory cytokines IL-12, TNF-α, and KC/GRO. The GC analysis revealed the presence of two PPARs agonist in sage MetOH extract. In vitro, the extract reduced in a dose-related manner the accumulation of lipid droplets; however no effect on lipolysis was observed. Conclusions Sage MetOH extract at low dose exhibits similar effects to rosiglitazone. It improves insulin sensitivity, inhibits lipogenesis in adipocytes and reduces inflammation as judged by plasma cytokines. Sage presents an alternative to pharmaceuticals for the treatment of diabetes and associated inflammation

IL-1β (interleukin-1β) stimulates the production and release of multiple cytokines and chemokines by human preadipocytes

The effect of IL-1β on cytokine and chemokine production by human preadipocytes has been examined. Preadipocytes were incubated with IL-1β and cytokine and chemokine release measured at 24 h by protein arrays, while the expression of cytokine/chemokine genes was assessed by qPCR at 4 and 24 h. IL-1β stimulated the secretion of multiple cytokines/chemokines, including IL-6, IL-8, IL-10, IL-13, MCP-4, TNFα and IP-10. IL-10 was not released by un-stimulated preadipocytes, while IL-6 exhibited the greatest response to IL-1β (453-fold increase). IL-16 and IL-12p40 did not respond to IL-1β. qPCR demonstrated that IL-1β markedly stimulated CCL3, CSF3 and CXCL10expression at 4 h (>900-fold mRNA increase). A time-course indicated that while CCL13 (encoding MCP-4) exhibited minimal basal expression in preadipocytes, expression increased progressively following differentiation. Human preadipocytes are highly sensitive to IL-1β, the cytokine stimulating a major inflammatory response in these cells similar to that in mature adipocytes

Etude numerique de la cinetique d'ionisation d'une vapeur alcaline par interaction laser resonnante

SIGLECNRS T 55747 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Evidence for Anti-inflammatory Effects and Modulation of Neurotransmitter Metabolism by Salvia Officinalis L.

Abstract Background: Cognitive health is of great interest to society, with neuroinflammation and systemic inflammation as age-related risk factors linked to declines in cognitive performance. Several botanical ingredients have been suggested to have benefits in this area including sage (Salvia officinalis), which has shown anti-inflammatory effects and exhibited promising cognitive improvements in multiple human studies. The current study aims to further investigate sage’s anti-inflammatory effects in human cells and uncover other relevant biological activities.Methods: The release of multiple Cytokine and Chemokines was measured in human primary intestinal epithelial cells treated with sage extract, with or without LPS stimulation, and Blood Brain Barrier (BBB) cells in presence or absence of recombinant IL-17A and/or Human IL-17RA/IL-17R Antibody. Antioxidant effects were also assessed in BBB cells incubated with the extract and H2O2. The anti-inflammatory effects of sage extract were further assessed based on clinically-relevant biomarker readouts across twelve human primary cell-based disease models of the BioMAP® Diversity PLUS® Panel. Results: Sage showed significant attenuation of the release of most cytokines/chemokines into apical media in LPS-stimulated intestinal cells, but small increases of in the release of markers including IL-6, IL-8 in basolateral media; where TNF-α was the only marker to be significantly reduced. Sage attenuated the release of CRP and VCAM-1 from BBB cells under IL-17A induced conditions, as well as the basal level of release of MCP-1, and also decreased H2O2 induced ROS overproduction in these cells. Phenotypic profiling with the BioMAP® Diversity PLUS® Panel identified additional anti-inflammatory mediators, and based on a similarity search analysis suggested potential mechanistic similarity to caffeic acid and drugs known to inhibit COMT and MAO activity to modulate monoamine metabolism. Subsequent in vitro assessment showed that sage was able to inhibit the activity of these same enzymes. Conclusions: Sage extract showed anti-inflammatory effects across multiple human cell lines, which could potentially reduce peripheral inflammation and support cognitive health. Sage extract also showed the ability to inhibit enzymes related to the metabolism of monoamine neurotransmitters, suggesting possible dopaminergic and serotonergic effects acting alongside proposed cholinergic effects to mediate acute cognitive performance benefits previously demonstrated for the extract.</jats:p

Evidence for anti-inflammatory effects and modulation of neurotransmitter metabolism by Salvia officinalis L.

Abstract Background Cognitive health is of great interest to society, with neuroinflammation and systemic inflammation age-related risk factors that are linked to declines in cognitive performance. Several botanical ingredients have been suggested to have benefits in this area including Salvia officinalis (sage), which has shown anti-inflammatory effects and exhibited promising cognitive improvements in multiple human studies. The current study demonstrates anti-inflammatory effects for S. officinalis across a broad set of in vitro models in human cells, and adds further evidence to support modulation of acetylcholine and monoamine neurostransmitter levels as mechanisms that contribute towards the benefits of the herb on cognitive health. Methods The effect of S. officinalis extract on release of multiple cytokines and chemokines was measured in human primary intestinal epithelial cells treated with or without LPS stimulation, and Blood Brain Barrier (BBB) cells in presence or absence of recombinant IL-17A and/or Human IL-17RA/IL-17R Antibody. Antioxidant effects were also assessed in BBB cells incubated with the extract and H2O2. The anti-inflammatory effects of S. officinalis extract were further assessed based on clinically-relevant biomarker readouts across 12 human primary cell-based disease models of the BioMAP Diversity PLUS panel. Results S. officinalis showed significant attenuation of the release of most cytokines/chemokines into apical media in LPS-stimulated intestinal cells, but small increases in the release of markers including IL-6, IL-8 in basolateral media; where TNF-α was the only marker to be significantly reduced. S. officinalis attenuated the release of CRP and VCAM-1 from BBB cells under IL-17A induced conditions, and also decreased H2O2 induced ROS overproduction in these cells. Phenotypic profiling with the BioMAP Diversity PLUS Panel identified additional anti-inflammatory mediators, and based on a similarity search analysis suggested potential mechanistic similarity to caffeic acid and drugs known to inhibit COMT and MAO activity to modulate monoamine metabolism. Subsequent in vitro assessment showed that S. officinalis was able to inhibit the activity of these same enzymes. Conclusions S. officinalis extract showed anti-inflammatory effects across multiple human cell lines, which could potentially reduce peripheral inflammation and support cognitive health. S. officinalis extract also showed the ability to inhibit enzymes related to the metabolism of monoamine neurotransmitters, suggesting possible dopaminergic and serotonergic effects acting alongside proposed cholinergic effects to mediate acute cognitive performance benefits previously demonstrated for the extract. </jats:sec