Tyrosine Phosphorylation in Immune Cells: Direct and Indirect Effects on Toll-Like Receptor-Induced Proinflammatory Cytokine Production

2009 ◽  
Vol 29 (4) ◽  
pp. 347-367 ◽  
Author(s):  
Pauline Johnson ◽  
Jennifer L. Cross
Keyword(s):  
Tyrosine Phosphorylation ◽  
Immune Cells ◽  
Indirect Effects ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Direct And Indirect Effects ◽  
Proinflammatory Cytokine Production ◽  
Toll Like Receptor

scholarly journals Toll-Like Receptor 6 Plays an Important Role in Host Innate Resistance to Brucella abortus Infection in Mice

2013 ◽  
Vol 81 (5) ◽  
pp. 1654-1662 ◽  
Author(s):  
Leonardo A. de Almeida ◽  
Gilson C. Macedo ◽  
Fábio A. V. Marinho ◽  
Marco T. R. Gomes ◽  
Patrícia P. Corsetti ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Brucella Abortus ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Innate Immune ◽  
Proinflammatory Cytokine Production ◽  
Toll Like Receptor ◽  
Content Type

ABSTRACTBrucella abortusis recognized by several Toll-like receptor (TLR)-associated pathways triggering proinflammatory responses that affect both the nature and intensity of the immune response. Previously, we demonstrated thatB. abortus-mediated dendritic cell (DC) maturation and control of infection are dependent on the adaptor molecule MyD88. However, the involvement of all TLRs in response toB. abortusinfection is not completely understood. Therefore, we decided to evaluate the requirement for TLR6 in host resistance toB. abortus. Here, we demonstrated that TLR6 is an important component for triggering an innate immune response againstB. abortus. Anin vitroluciferase assay indicated that TLR6 cooperates with TLR2 to senseBrucellaand further activates NF-κB signaling. However,in vivoanalysis showed that TLR6, not TLR2, is required for the efficient control ofB. abortusinfection. Additionally,B. abortus-infected dendritic cells require TLR6 to induce tumor necrosis factor alpha (TNF-α) and interleukin-12 (IL-12). Furthermore, our findings demonstrated that the mitogen-activated protein kinase (MAPK) signaling pathway is impaired in TLR2, TLR6, and TLR2/6 knockout (KO) DCs when infected withB. abortus, which may account for the lower proinflammatory cytokine production observed in TLR6 KO mouse dendritic cells. In summary, the results presented here indicate that TLR6 is required to trigger innate immune responses againstB. abortusin vivoand is required for the full activation of DCs to induce robust proinflammatory cytokine production.

Abatacept modulates proinflammatory macrophage responses upon cytokine-activated T cell and Toll-like receptor ligand stimulation

2011 ◽  
Vol 71 (1) ◽  
pp. 80-83 ◽  
Author(s):  
M H Wenink ◽  
K C M Santegoets ◽  
A M Platt ◽  
W B van den Berg ◽  
P L C M van Riel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Proinflammatory Cytokine Production ◽  
Toll Like Receptor ◽  
Activated T Cells ◽  
Activated T Cell ◽  
Ligand Stimulation

ObjectivesWe investigated whether Abatacept might reduce proinflammatory cytokine production by macrophages upon contact with cytokine activated T cells and/or stimulation with TLR ligands.MethodsMacrophages and cytokine stimulated T cells (Tck) were added together in the presence of Abatacept or a control Ig, with or without TLR ligands. The production of cytokines was determined by luminex.ResultsAbatacept reduced Tck-induced production of TNFa by macrophages. Tck and TLR ligands synergistically induced the production of proinflammatory cytokines by macrophages, especially IL-12p70. The production of IL-12p70 coincided with the production of IFNg, which were both reduced in the presence of Abatacept.ConclusionsTck induce the production of TNFa by macrophages and facilitate the highly increased production of proinflammatory cytokines in the presence of TLR ligands. Abatacept was shown to potently suppress these pathways suggesting that its role may extend beyond antigen specific T cell mediated effector function.

scholarly journals Toll-Like Receptor 7 Agonist Therapy with Imidazoquinoline Enhances Cancer Cell Death and Increases Lymphocytic Infiltration and Proinflammatory Cytokine Production in Established Tumors of a Renal Cell Carcinoma Mouse Model

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Eric C. Kauffman ◽  
Huixian Liu ◽  
Michael J. Schwartz ◽  
Douglas S. Scherr
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Death ◽  
T Cell ◽  
Tumor Growth ◽  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Serum Levels ◽  
Proinflammatory Cytokine Production ◽  
Toll Like Receptor

Imidazoquinolines are synthetic toll-like receptor 7 and 8 agonists and potent dendritic cell activators with established anticancer activity. Here we test the hypothesis that imidazoquinoline hasin vivoefficacy within established renal cell carcinoma (RCC) tumors. Immunocompetent mice bearing syngeneic RCC xenografts were treated with imidazoquinoline or placebo at two separate time points. Harvested tumors were assayed by TUNEL/caspase-3/Ki67 immunostains to evaluate cell death/apoptosis/proliferation, and CD3/B220/CD45 immunostains to evaluate T-cell lymphocyte/B-cell lymphocyte/pan-leukocyte tumor infiltration. ELISA measurement of tumor and serum levels of proinflammatory cytokines, IL-6 and MCP-1, was performed. A single imidazoquinoline dose significantly decreased RCC tumor growth by 50% and repeat dosing compounded the effect, without observed weight loss or other toxicity. Tumor immunostaining revealed significant increases in cell death and apoptosis without changes in cell proliferation, supporting induction of apoptosis as the primary mechanism of tumor growth suppression. Imidazoquinoline treatment also significantly enhanced peritumoral aggregation and intratumoral infiltration by T-cell lymphocytes, while increasing intratumoral (but not serum) levels of proinflammatory cytokines. In conclusion, imidazoquinoline treatment enhances T-cell lymphocyte infiltration and proinflammatory cytokine production within established mouse RCC tumors, while suppressing tumor growth via induction of cancer cell apoptosis. These findings support a therapeutic role for imidazoquinoline in RCC.

scholarly journals Differential Regulation of Toll-Like Receptor-Mediated Cytokine Production by Unfolded Protein Response

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Sena Kim ◽  
Yeonsoo Joe ◽  
Young-Joon Surh ◽  
Hun Taeg Chung
Keyword(s):  
Er Stress ◽  
Unfolded Protein Response ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Inflammatory Diseases ◽  
Proinflammatory Cytokine Production ◽  
Toll Like Receptor ◽  
Unfolded Protein ◽  
Nf Kappab ◽  
Protein Response

The ability of the host immune response is largely mediated by the proinflammatory cytokine production. Physiological and pathological conditions of endoplasmic reticulum (ER) trigger unfolded protein response and contribute to the development or pathology of inflammatory diseases. Under ER stress, unfolded protein response (UPR) signaling pathways participate in upregulating inflammatory cytokine production via NF-kappaB, MAPK, and GSK-3β. Moreover, it has been suggested that ER stress crosstalks with toll-like receptor (TLR) signaling pathway to promote the production of proinflammatory cytokines. In addition, TLR stimulation can lead to UPR activation to promote inflammation. In this review, we will cover how proinflammatory cytokine production by UPR signaling can be induced or amplified in the presence or absence of TLR activation.

scholarly journals Signaling via Toll-Like Receptor 5 Can Initiate Inflammatory Mediator Production by Murine Osteoblasts

2003 ◽  
Vol 71 (9) ◽  
pp. 5418-5421 ◽  
Author(s):  
Denise R. Madrazo ◽  
Susanne L. Tranguch ◽  
Ian Marriott
Keyword(s):  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Inflammatory Mediator ◽  
Bacterial Pathogens ◽  
Transcriptional Regulators ◽  
Proinflammatory Cytokine Production ◽  
Toll Like Receptor ◽  
Bone Infections ◽  
Inflammatory Mediator Production ◽  
Toll Like Receptor 5

ABSTRACT Murine osteoblasts express Toll-like receptor 5 (TLR5), and this expression is upregulated following exposure to bacteria or to the TLR5 agonist, flagellin. Importantly, flagellin activates transcriptional regulators and elicits proinflammatory cytokine production, suggesting TLR5 functionality. TLR5 may represent an important mechanism underlying the recognition of bacterial pathogens by osteoblasts during bone infections.

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