MicroRNA-29a regulates pro-inflammatory cytokine secretion and scavenger receptor expression by targeting LPL in oxLDL-stimulated dendritic cells

FEBS Letters ◽  
2011 ◽  
Vol 585 (4) ◽  
pp. 657-663 ◽  
Author(s):  
Ting Chen ◽  
Zhoubin Li ◽  
Jing Tu ◽  
Weiguo Zhu ◽  
Junhua Ge ◽  
...  
2019 ◽  
Vol 10 ◽  
Author(s):  
Stefania De Santis ◽  
Grazia Serino ◽  
Maria R. Fiorentino ◽  
Vanessa Galleggiante ◽  
Patrizia Gena ◽  
...  

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 355 ◽  
Author(s):  
Moeller ◽  
Wolfheimer ◽  
Goretzki ◽  
Scheurer ◽  
Schülke

Fusion proteins incorporating the TLR5-ligand flagellin are currently undergoing clinical trials as vaccine candidates for many diseases. We recently reported a flagellin:allergen fusion protein containing the TLR5-ligand flagellin A (FlaA) from Listeria monocytogenes and the major birch pollen allergen Bet v 1 (rFlaA:Betv1) to prevent allergic sensitization in an experimental mouse model. This study analyzes the signaling pathways contributing to rFlaA:Betv1-mediated pro- and anti-inflammatory cytokine secretion and cell metabolism in myeloid dendritic cells (mDCs) in vitro. The influence of mammalian target of rapamycin (mTOR)-, NF?B-, and MAP kinase (MAPK)-signaling on cytokine secretion and metabolic activity of bone marrow (BM)-derived mDCs stimulated with rFlaA:Betv1 were investigated by pre-treatment with either mTOR- (rapamycin), NF?B- (dexamethason, BMS-345541, TPCA-1, triptolide, or BAY-11) or MAPK- (SP600125, U0126, or SB202190) inhibitors, respectively. rFlaA:Betv1-mediated IL-10 secretion as well as activation of mDC metabolism, rather than pro-inflammatory cytokine secretion, were inhibited by rapamycin. Inhibition of NFκB-signaling suppressed rFlaA:Betv1-induced IL-12, while inhibition of MAPK-signaling dose-dependently suppressed rFlaA:Betv1-induced IL-10 as well as pro-inflammatory IL-6 and TNF-α production. Notably, with the exception of a partial JNK-dependency, rFlaA:Betv1-mediated effects on mDC metabolism were mostly NF?B- and MAPK-independent. Therefore, MAPK-mediated activation of both NFκB- and mTOR-signaling likely is a key pathway for the production of pro- and anti-inflammatory cytokines by flagellin fusion protein vaccines.


Blood ◽  
2006 ◽  
Vol 109 (8) ◽  
pp. 3316-3324 ◽  
Author(s):  
Hiroyuki Kishimoto ◽  
Toshiaki Ohteki ◽  
Nobuyuki Yajima ◽  
Koichi Kawahara ◽  
Miyuki Natsui ◽  
...  

Abstract The tumor suppressor PTEN is mutated in many human cancers. We previously used the Cre-loxP system to generate mice (LckCrePten mice) with a Pten mutation in T-lineage cells. Here we describe the phenotype of Pten-deficient Vα14iNKT cells. A failure in the development of Vα14iNKT cells occurs in the LckCrePten thymus between stage 2 (CD44highNK1.1−) and stage 3 (CD44highNK1.1+), resulting in decreased numbers of peripheral Vα14iNKT cells. In vitro, Pten-deficient Vα14iNKT cells show reduced proliferation and cytokine secretion in response to αGalCer stimulation but enhanced inhibitory Ly49 receptor expression. Following interaction with dendritic cells (DCs) loaded with αGalCer, Pten-deficient Vα14iNKT cells demonstrate activation of PI3K. Indeed, the effects of the Pten mutation require intact function of the PI3K subunits p110γ and p110δ. In vivo, LckCrePten mice display reduced serum IFNγ after αGalCer administration. Importantly, Vα14iNKT cell–mediated protection against the metastasis of melanoma cells to the lung was impaired in the absence of Pten. Thus, the Pten/PI3K pathway is indispensable for the homeostasis and antitumor surveillance function of Vα14iNKT cells.


FEBS Letters ◽  
2011 ◽  
Vol 585 (3) ◽  
pp. 567-573 ◽  
Author(s):  
Ting Chen ◽  
Zhoubin Li ◽  
Tu jing ◽  
Weiguo Zhu ◽  
Junhua Ge ◽  
...  

2018 ◽  
Vol 9 ◽  
Author(s):  
Stefania De Santis ◽  
Grazia Serino ◽  
Maria R. Fiorentino ◽  
Vanessa Galleggiante ◽  
Patrizia Gena ◽  
...  

FEBS Open Bio ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1492-1502 ◽  
Author(s):  
Gyöngyike Emese Majai ◽  
Péter Gogolák ◽  
Márta Tóth ◽  
Judit Hodrea ◽  
Dorottya Horváth ◽  
...  

2020 ◽  
Vol 90 (1-2) ◽  
pp. 103-112 ◽  
Author(s):  
Michael J. Haas ◽  
Marilu Jurado-Flores ◽  
Ramadan Hammoud ◽  
Victoria Feng ◽  
Krista Gonzales ◽  
...  

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.


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