Tumor necrosis factor-α causes release of cytosolic interleukin-18 from human neutrophils

Silliman, Christopher C.; Kelher, Marguerite; Gamboni‐Robertson, Fabia; Hamiel, Christine; England, Kelly M.; Dinarello, Charles A.; Wyman, Travis H.; Khan, Samina Y.; McLaughlin, Nathan; Bercovitz, Rachel S.; Banerjee, Anirban

doi:10.1152/ajpcell.00011.2009

Cited by 12 publications

(12 citation statements)

References 68 publications

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“…In accordance with previous studies, mature IL-18 was only transiently detectable in neutrophil supernatants (22), despite that TLR stimulation upregulated intracellular pro-IL-18 in neutrophils. This may be the result of neutrophil reuptake of released IL-18 or degradation by released proteases.…”

Section: Discussionsupporting

confidence: 92%

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TLR-Stimulated Neutrophils Instruct NK Cells To Trigger Dendritic Cell Maturation and Promote Adaptive T Cell Responses

Riise

Bernson

Aurelius

et al. 2015

The Journal of Immunology

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Polymorphonuclear neutrophils (PMNs) are innate effector cells with pivotal roles in pathogen recognition, phagocytosis, and eradication. However, their role in the development of subsequent immune responses is incompletely understood. This study aimed to identify mechanisms of relevance to the cross talk between human neutrophils and NK cells and its potential role in promoting adaptive immunity. TLR-stimulated PMNs were found to release soluble mediators to attract and activate NK cells in vitro. PMN-conditioned NK cells displayed enhanced cytotoxicity and cytokine production, and responded vigorously to ensuing stimulation with exogenous and endogenous IL-12. The neutrophil-induced activation of NK cells was prevented by caspase-1 inhibitors and by natural antagonists to IL-1 and IL-18, suggesting a role for the NOD-like receptor family pyrin domain containing-3 inflammasome. In addition, PMN-conditioned NK cells triggered the maturation of monocyte-derived dendritic cells, which promoted T cell proliferation and IFN-γ production. These data imply that neutrophils attract NK cells to sites of infection to convert these cells into an active state, which drives adaptive immune responses via maturation of dendritic cells. Our results add to a growing body of evidence that suggests a sophisticated role for neutrophils in orchestrating the immune response to pathogens.

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Section: Discussionsupporting

confidence: 92%

“…These contradictory results regarding IL-18 incited us to perform additional experiments. Short-time stimulation with Clo97 triggered IL-18 secretion by PMNs; but in agreement with previous studies (22), the concentration of IL-18 rapidly returned to baseline levels (Fig. 6D).…”

Section: Neutrophil Conditioning Of Nk Cells Is Caspase Dependent Andsupporting

confidence: 92%

TLR-Stimulated Neutrophils Instruct NK Cells To Trigger Dendritic Cell Maturation and Promote Adaptive T Cell Responses

Riise

Bernson

Aurelius

et al. 2015

The Journal of Immunology

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“…32 It has been reported that TNF- induced insulin resistance is associated with an elevated expression of IL-18 in human skeletal muscle tissue, which suggest, a possible role for IL-18 in the pathogenesis of TNF- induced insulin resistance in humans. 33,34 Also, it has been reported that antiinflammatory cytokines (IL-4, IL-10, IL-13, etc) counteracts the cytotoxic effects of proinflammatory cytokines, i.e. IL-1, TNF-, IL-17, etc in insulin-producing cells through the reduction of nitrosative stress.…”

Section: Discussionmentioning

confidence: 99%

Incretin Hormones and Insulin Responses During OGTT in Newly Diagnosed T2DM Patients

Jhuma

Giasuddin

Haque³

et al. 2018

Bangladesh Med Res Counc Bull

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Several research groups have reported variable results about incretin effects of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1(GLP-1) particularly, as well as cytokines balance in type 2 diabetes mellitus (T2DM). The present case-control prospective interventional study was conducted in 2014-2015 at Medical College for Women & Hospital, Dhaka, investigating responses of incretin hormones and insulin to oral glucose tolerance test (OGTT) in Bangladeshi subjects. Blood samples were collected from 36 OGTT positive adult T2DM patients (Pt) and 30 normal adults (NC) at '0' minute (fasting) and at 2 hours after OGTT. Routine laboratory investigations in blood were done and special parameters in serum, i.e. insulin, HGH, TSH, GIP and GLP-1 were analyzed using enzyme immunoassay kits. Pt had FBG and BG2Hr levels much higher than NC (p<0.001). In Pt, F-Insulin and Insulin2Hr were much lower than NC subjects (p<0.001), although Insulin2Hr level was higher than F-Insulin level in Pt. F-GIP (p=0.309) and F-GLP-1(p=0.984) levels were similar between Pt and NC. Interestingly, NC responded to OGTT by increasing GIP2Hr and GLP-1,2Hr levels about 3 times, whereas Pt responded by raising about 1.5 times only compared to F-GIP and F-GLP-1 (p< 0.001). Reduced insulin levels, both fasting and postprandial, were possibly due to decreased responses of GIP and GLP-1 to glucose load in T2DM patients. Further studies with a larger sample size including cytokines are warranted.

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“…Hence, to gain insight into the neutrophil molecules involved in the activation of γδ T cells, we searched for factors secreted by activated neutrophils, which could play a role in the activation of T cells. Among these molecules, IL‐18 is an inflammatory cytokine produced by neutrophils in response to stimulation by TNF‐ α that promotes both the proliferation of CD8 + T cells stimulated by anti‐CD3 antibodies, and the expansion of natural killer cells in the presence of IL‐2 . Moreover, it was reported that IL‐18 stimulates the proliferation of γδ T cells activated by IL‐2 and zoledronate, and the blockade of the IL‐18R α chain strongly inhibits the proliferation of γδ T cells, suggesting the involvement of IL‐18 signalling .…”

Section: Resultsmentioning

confidence: 99%

Modulation of γδ T‐cell activation by neutrophil elastase

et al. 2017

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γδ T cells are non-conventional, innate-like T cells, characterized by a restricted T-cell receptor repertoire. They participate in protective immunity responses against extracellular and intracellular pathogens, tumour surveillance, modulation of innate and adaptive immune responses, tissue healing, epithelial cell maintenance and regulation of physiological organ function. In this study, we investigated the role of neutrophils during the activation of human blood γδ T cells through CD3 molecules. We found that the up-regulation of CD69 expression, and the production of interferon-γ and tumour necrosis factor-α induced by anti-CD3 antibodies was potentiated by neutrophils. We found that inhibition of caspase-1 and neutralization of interleukin-18 did not affect neutrophil-mediated modulation. By contrast, the treatment with serine protease inhibitors prevented the potentiation of γδ T-cell activation induced by neutrophils. Moreover, the addition of elastase to γδ T-cell culture increased their stimulation, and the treatment of neutrophils with elastase inhibitor prevented the effect of neutrophils on γδ T-cell activation. Furthermore, we demonstrated that the effect of elastase on γδ T cells was mediated through the protease-activated receptor, PAR1, because the inhibition of this receptor with a specific antagonist, RWJ56110, abrogated the effect of neutrophils on γδ T-cell activation.

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Tumor necrosis factor-α causes release of cytosolic interleukin-18 from human neutrophils

Abstract: A. Tumor necrosis factor-␣ causes release of cytosolic interleukin-18 from human neutrophils.

Cited by 12 publications

References 68 publications

TLR-Stimulated Neutrophils Instruct NK Cells To Trigger Dendritic Cell Maturation and Promote Adaptive T Cell Responses

TLR-Stimulated Neutrophils Instruct NK Cells To Trigger Dendritic Cell Maturation and Promote Adaptive T Cell Responses

Incretin Hormones and Insulin Responses During OGTT in Newly Diagnosed T2DM Patients

Modulation of γδ T‐cell activation by neutrophil elastase

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