Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells

Dichlberger, Andrea; Schlager, Stefanie; Maaninka, Katariina; Schneider, Wolfgang J.; Kovanen, Petri T.

doi:10.1194/jlr.m048553

Cited by 98 publications

(91 citation statements)

References 31 publications

(37 reference statements)

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“…We found that iPTH treatment upregulates the nuclear translocation of NFAT1/2 and SMAD2/3 and the binding of NFAT1/2 and SMAD3 to the Wnt10b promoter in BM CD8+ T cells. As previously reported for other promoters (Dichlberger, Schlager et al, 2014, Tone, Furuuchi et al, 2008 Tregs suppress conventional T cell activation through a multitude of mechanisms (Shevach, 2009), including the blunting of CD28 signaling in CD8+ T cells (Wing et al, 2008). Accordingly, we found that iPTH lessen CD80/CD86 expression on antigen presenting cells, thereby reducing CD28 signaling in conventional BM CD8+ T cells.…”

Section: Cd25supporting

confidence: 56%

Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH ‐induced bone anabolism in mice

D’Amelio

Tyagi

et al. 2017

EMBO Reports

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Teriparatide is a bone anabolic treatment for osteoporosis, modeled in animals by intermittent PTH (iPTH) administration. iPTH-induced bone anabolism involves CD8+ T cell production of the osteogenic Wnt ligand Wnt10b, induced via yet unknown mechanisms. Here we show that Teriparatide and iPTH cause a ~2-3-fold increase in the number of regulatory T cells (Tregs) in humans and mice. Attesting in vivo relevance, blockade of the Treg increase in mice prevents iPTH-induced CD8+ T cell Wnt10b production and bone anabolism. Mechanistically, Treg action on CD8+ T cells promotes binding of NFAT1/2 and SMAD3 complexes to a NFAT/SMADactivated Wnt10b promoter region that stimualtes Wnt10b gene expression in CD8+ T cells.

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Section: Cd25supporting

confidence: 56%

Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH ‐induced bone anabolism in mice

D’Amelio

Tyagi

et al. 2017

EMBO Reports

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“…CD4 + T cells exhibit similarly polarized metabolic programs as they differentiate into effector T cells, fueled by glucose, or into regulatory T‐cells, fueled by fatty acid β‐oxidation (Michalek et al , ). Finally, a study in mast cells demonstrated that droplets can also serve as the main storage site for arachidonic acid, which is the precursor to eicosanoid hormones such as the prostaglandins and leukotrienes that regulate inflammation and vasodilation (Dichlberger et al , ).…”

Section: Lipid Droplets and Infectious Diseasementioning

confidence: 99%

The assembly of lipid droplets and their roles in challenged cells

2018

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Cytoplasmic lipid droplets are important organelles in nearly every eukaryotic and some prokaryotic cells. Storing and providing energy is their main function, but they do not work in isolation. They respond to stimuli initiated either on the cell surface or in the cytoplasm as conditions change. Cellular stresses such as starvation and invasion are internal insults that evoke changes in droplet metabolism and dynamics. This review will first outline lipid droplet assembly and then discuss how droplets respond to stress and in particular nutrient starvation. Finally, the role of droplets in viral and microbial invasion will be presented, where an unresolved issue is whether changes in droplet abundance promote the invader, defend the host, to try to do both. The challenges of stress and infection are often accompanied by changes in physical contacts between droplets and other organelles. How these changes may result in improving cellular physiology, an ongoing focus in the field, is discussed.

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“…To determine if this was the case, we first investigated the effect of Resveratrol on expression of the cyclooxygenases COX-1 and COX-2, key enzymes involved in the conversion of arachidonic acid to prostaglandins [31,32]. Both COX-1 and COX-2 are involved in PGD 2 biosynthesis.…”

Section: Resultsmentioning

confidence: 99%

Resveratrol preferentially inhibits IgE-dependent PGD2 biosynthesis but enhances TNF production from human skin mast cells

Shirley

McHale

Gomez

2016

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background Resveratrol, a natural polyphenol found in the skin of red grapes, is reported to have anti-inflammatory properties including protective effects against aging. Consequently, Resveratrol is a common nutritional supplement and additive in non-prescription lotions and creams marketed as anti-aging products. Studies in mice and with mouse bone marrow-derived mast cells (BMMCs) have indicated anti-allergic effects of Resveratrol. However, the effects of Resveratrol on human primary mast cells have not been reported. Methods Human mast cells were isolated and purified from normal skin tissue of different donors. The effect of Resveratrol on IgE-dependent release of allergic inflammatory mediators was determined using various immunoassays, Western blotting, and quantitative real-time PCR. Results Resveratrol at low concentrations (≤ 10 µM) inhibited PGD2 biosynthesis but not degranulation. Accordingly, COX-2 expression was inhibited but phosphorylation of Syk, Akt, p38, and p42/44 (ERKs) remained intact. Surprisingly, TNF production was significantly enhanced with Resveratrol. At high a concentration (100 µM), Resveratrol significantly inhibited all parameters analyzed except Syk phosphorylation. Conclusions Here, we show that Resveratrol at low concentrations exerts its anti-inflammatory properties by preferentially targeting the arachidonic acid pathway. We also demonstrate a previously unrecognized pro-inflammatory effect of Resveratrol – the enhancement of TNF production from human mature mast cells following IgE-dependent activation. General significance These findings suggest that Resveratrol as a therapeutic agent could inhibit PGD2-mediated inflammation but would be ineffective against histamine-mediated allergic reactions. However, Resveratrol could potentially exacerbate or promote allergic inflammation by enhancing IgE-dependent TNF production from mast cells in human skin.

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Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells

Cited by 98 publications

References 31 publications

Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH ‐induced bone anabolism in mice

Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH ‐induced bone anabolism in mice

The assembly of lipid droplets and their roles in challenged cells

Resveratrol preferentially inhibits IgE-dependent PGD2 biosynthesis but enhances TNF production from human skin mast cells

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