scholarly journals NFκB- and MAP-Kinase Signaling Contribute to the Activation of Murine Myeloid Dendritic Cells by a Flagellin A:Allergen Fusion Protein

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 355 ◽  
Author(s):  
Moeller ◽  
Wolfheimer ◽  
Goretzki ◽  
Scheurer ◽  
Schülke
Keyword(s):  
Dendritic Cells ◽  
Fusion Protein ◽  
Map Kinase ◽  
Inflammatory Cytokine ◽  
Allergic Sensitization ◽  
Birch Pollen ◽  
Mapk Signaling ◽  
Cytokine Secretion ◽  
Myeloid Dendritic Cells ◽  
Anti Inflammatory

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.

scholarly journals CD1d on Myeloid Dendritic Cells Stimulates Cytokine Secretion from and Cytolytic Activity of Vα24JαQ T Cells: A Feedback Mechanism for Immune Regulation

2000 ◽  
Vol 165 (7) ◽  
pp. 3756-3762 ◽  
Author(s):  
Otto O. Yang ◽  
Frederick K. Racke ◽  
Phuong Thi Nguyen ◽  
Rudolf Gausling ◽  
Michael E. Severino ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Regulation ◽  
Feedback Mechanism ◽  
Cytolytic Activity ◽  
Cytokine Secretion ◽  
Myeloid Dendritic Cells

CD163 levels, pro- and anti-inflammatory cytokine secretion of monocytes in children with pulmonary tuberculosis

2016 ◽  
Vol 52 (5) ◽  
pp. 675-683 ◽  
Author(s):  
Esin Aktas Cetin ◽  
Leyla Pur Ozyigit ◽  
Yusuf Metin Gelmez ◽  
Erkan Cakir ◽  
Ahmet Hakan Gedik ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Inflammatory Cytokine ◽  
Cytokine Secretion ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

scholarly journals Anti-Inflammatory Effects of Saccharomyces Boulardii on Myeloid Dendritic Cells From Patients With Crohn's Disease and Ulcerative Colitis

2011 ◽  
Vol 140 (5) ◽  
pp. S-849
Author(s):  
Saskia Thomas ◽  
Diana Metzke ◽  
Yvonne Dörffel ◽  
Jürgen Schmitz ◽  
Andreas Radbruch ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dendritic Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Saccharomyces Boulardii ◽  
Myeloid Dendritic Cells ◽  
Anti Inflammatory

scholarly journals Corrigendum: Aquaporin-9 Contributes to the Maturation Process and Inflammatory Cytokine Secretion of Murine Dendritic Cells

2019 ◽  
Vol 10 ◽  
Author(s):  
Stefania De Santis ◽  
Grazia Serino ◽  
Maria R. Fiorentino ◽  
Vanessa Galleggiante ◽  
Patrizia Gena ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inflammatory Cytokine ◽  
Cytokine Secretion ◽  
Maturation Process ◽  
Aquaporin 9

scholarly journals Prototypical anti-inflammatory cytokine IL-10 prevents loss of IGF-I-induced myogenin protein expression caused by IL-1β

2008 ◽  
Vol 294 (4) ◽  
pp. E709-E718 ◽  
Author(s):  
Klemen Strle ◽  
Robert H. McCusker ◽  
Rodney W. Johnson ◽  
Samantha M. Zunich ◽  
Robert Dantzer ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Muscle Wasting ◽  
Inflammatory Responses ◽  
Mapk Signaling ◽  
Protective Role ◽  
Igf I ◽  
Anti Inflammatory ◽  
Kinase Pathway ◽  
Anti Inflammatory Cytokine

Prolonged and excessive inflammation is implicated in resistance to the biological actions of IGF-I and contributes to the pathophysiology of neurodegenerative, metabolic, and muscle-wasting disorders. IL-10 is a critical anti-inflammatory cytokine that restrains inflammatory responses in macrophages and T cells by inhibiting cytokine and chemokine synthesis and reducing expression of their receptors. Here we demonstrate that IL-10 plays a protective role in nonhematopoietic cells by suppressing the ability of exogenous IL-1β to inhibit IGF-I-induced myogenin and myosin heavy chain expression in myoblasts. This action of IL-10 is not caused by impairment of IL-1β-induced synthesis of IL-6 or the ability of IL-1β to activate two members of the MAPK family, ERK1/2 and p38. Instead, this newly defined protective role of IL-10 occurs by specific reversal of IL-1β activation of the JNK kinase pathway. IL-10 blocks IL-1β-induced phosphorylation of JNK, but not ERK1/2 or p38, indicating that only the JNK component of the IL-1β-induced MAPK signaling pathway is targeted by IL-10. This conclusion is supported by the finding that a specific JNK inhibitor acts similarly to IL-10 to restore IGF-I-induced myogenin expression, which is suppressed by IL-1β. Collectively, these data demonstrate that IL-10 acts in a novel, nonclassical, protective manner in nonhematopoietic cells to inhibit the IL-1β receptor-induced JNK kinase pathway, resulting in prevention of IGF-I resistance.

scholarly journals Potential role of MRN-100, an iron-based compound, in upregulating production of cytokine IL-10 in human dendritic cells to promote an anti-inflammatory response in vitro

2019 ◽  
Vol 33 ◽  
pp. 205873841984493
Author(s):  
Mamdooh H Ghoneum ◽  
James K Gimzewski ◽  
Aya D Ghoneum ◽  
Sudhanshu Agrawal
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Inflammatory Cytokine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Functional Assay ◽  
Iron Based ◽  
Anti Inflammatory ◽  
Human Dendritic Cells

The hydroferrate fluid MRN-100, an iron-based compound with potent antioxidant characteristics, was examined to identify its possible anti-inflammatory effects on human dendritic cells (DCs) in vitro. Human monocyte–derived DCs were treated with MRN-100 at two concentrations (50 and 100 μL/mL) for 24 h and then stimulated with or without lipopolysaccharides (LPS). The expression of DC maturation markers was assessed by flow cytometry and the production of cytokines was determined by enzyme-linked immunosorbent assay (ELISA). Functional assay was performed by co-culturing MRN-100-treated and untreated DCs with allogeneic naïve CD4+ T cells and assaying the T cells’ cytokine production. Results show that treatment with MRN-100 significantly upregulated the co-stimulatory molecules CD80 and CD86 and increased human leukocyte antigen-DR (HLA-DR) though not significantly. MRN-100 treatment also significantly increased the production of the anti-inflammatory cytokine interleukin (IL)-10. On the other hand, MRN-100 significantly induced the secretion of pro-inflammatory cytokines such as IL-6 only at high concentrations. Furthermore, DCs pretreated with MRN-100 and either stimulated or not with LPS were able to prime CD4+ T cells to secrete significant amounts of IL-10 while inhibiting the secretion of pro-inflammatory cytokine tumor necrosis factor (TNF)-α. These results indicate that MRN-100 is a powerful anti-inflammatory agent that promotes the generation of an anti-inflammatory immune response in vitro. MRN-100 could be beneficial for treating patients with inflammatory diseases, including arthritis and type 1 diabetes, and its potential benefits should be examined in clinical trials.

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