Human Cord Blood-Derived Mast Cells Are Activated by the Nod1 Agonist M-TriDAP to Release Pro-Inflammatory Cytokines and Chemokines

Enoksson, Mattias; Ejendal, Karin F.K.; McAlpine, Sarah M.; Nilsson, Gunnar; Lunderius-Andersson, Carolina

doi:10.1159/000321933

Cited by 48 publications

(39 citation statements)

References 84 publications

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“…Recently, we demonstrated a specific role of Nod1 in the development of acute vascular inflammation in young mice (13) and atherosclerosis in adult mice (14). On the other hand, the effects of the activation of Nod1 in the fetuses or in newborns have been poorly understood (15)(16)(17). In the current study, we found that activation of Nod1 signaling in pregnant mice induced IUGR and IUFD.…”

supporting

confidence: 54%

Activation of Nod1 Signaling Induces Fetal Growth Restriction and Death through Fetal and Maternal Vasculopathy

Inoue

Nishio

Takada

et al. 2016

The Journal of Immunology

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Intrauterine fetal growth restriction (IUGR) and death (IUFD) are both serious problems in the perinatal medicine. Fetal vasculopathy is currently considered to account for a pathogenic mechanism of IUGR and IUFD. We previously demonstrated that an innate immune receptor, the nucleotide-binding oligomerization domain-1 (Nod1), contributed to the development of vascular inflammations in mice at postnatal stages. However, little is known about the deleterious effects of activated Nod1 signaling on embryonic growth and development. We report that administration of FK565, one of the Nod1 ligands, to pregnant C57BL/6 mice induced IUGR and IUFD. Mass spectrometry analysis revealed that maternally injected FK565 was distributed to the fetal tissues across placenta. In addition, maternal injection of FK565 induced robust increases in the amounts of CCL2, IL-6, and TNF proteins as well as NO in maternal, placental and fetal tissues. Nod1 was highly expressed in fetal vascular tissues, where significantly higher levels of CCL2 and IL-6 mRNAs were induced with maternal injection of FK565 than those in other tissues. Using Nod1-knockout mice, we verified that both maternal and fetal tissues were involved in the development of IUGR and IUFD. Furthermore, FK565 induced upregulation of genes associated with immune response, inflammation, and apoptosis in fetal vascular tissues. Our data thus provided new evidence for the pathogenic role of Nod1 in the development of IUGR and IUFD at the maternal-fetal interface.

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supporting

confidence: 54%

Activation of Nod1 Signaling Induces Fetal Growth Restriction and Death through Fetal and Maternal Vasculopathy

Inoue

Nishio

Takada

et al. 2016

The Journal of Immunology

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“…39 Human cord blood-derived human mast cells were generated as previously described. 40 Bone marrow from TNF Ϫ/Ϫ mice was a kind gift from Kerstin Steinbrink (Johannes GutenbergUniversität, Mainz, Germany). Peritoneal cavity mast cells (PCMCs) were generated by obtaining peritoneal cells from C57BL/6 mice by PBSflushing and subsequent culturing in OptiMEM supplemented with 10% FCS, 1% PeSt, 1% L-glutamine, and 4% SCF conditioned medium for 30 days.…”

Section: Cell Cultures and Experimental Animalsmentioning

confidence: 99%

Intraperitoneal influx of neutrophils in response to IL-33 is mast cell–dependent

Enoksson

Möller-Westerberg

Wicher

et al. 2013

Blood

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Key Points• IL-33-induced neutrophil recruitment in vivo is mast celldependent. This is partly mediated through the mast cell release of TNF-␣.• IL-33-treated human mast cells induce neutrophil migration in vitro. IL-33 is a recently discovered cytokine involved in induction of IntroductionIL-33 is a recently described cytokine of the IL-1 family that is expressed by a variety of cell types, most notably by epithelial and endothelial cells. 1 IL-33 promotes Th2 responses 2,3 and has been suggested to function as an alarmin when released on necrosis. 4-7 IL-33 is inactivated during apoptosis, 8 and unlike IL-1␤ and IL-18, it does not require proteolytical processing for activation. 4,9 Recently, we demonstrated that of all endogenous compounds released on necrosis, IL-33 alone is a key alarmin responsible for mast-cell activation. 5 Furthermore, IL-33 has emerged as a potent regulator of mast cell activity; inducing cytokine release, adhesion, maturation, and IgE-mediated degranulation. [10][11][12][13][14][15][16][17] In addition to mast cells, IL-33 activates several other cell types by signaling through the IL-33 receptor (IL-33R), including eosinophils, 18-20 basophils, 21-24 and dendritic cells. [25][26][27] Furthermore, a new family of IL-33R-positive innate lymphoid cells, including nuocytes, has been described during the last years. 28 Moreover, IL-33 has been implicated in the pathogenesis of several diseases (reviewed by Liew et al 1 ), including asthma 29,30 and arthritis. 31,32 Importantly, mast cells might have a central role in IL-33-associated diseases, as IL-33 for instance has been shown to exacerbate collagen-induced arthritis through a mast celldependent mechanism. 32 On the other hand, IL-33 has been ascribed several beneficial functions, including a cardioprotective function, 33 a protective role in atherosclerosis, 34 as well as an important role in helminth infections. 3 Thus, IL-33, similar to mast cells, exerts beneficial or detrimental effects depending on the local environment, which makes IL-33 an interesting cytokine with therapeutic potential.Despite this accumulated knowledge, much remains to be investigated regarding IL-33 functions in vivo. It was previously reported that IL-33 participates in the recruitment of mononuclear cells, 35 and a recent study reported that mice injected intravenously with IL-33 before cecal ligation and puncture recruited more neutrophils to the peritoneum than did mice treated with PBS, 36 thus displaying a reduced sepsis mortality rate.In this study we investigated the cellular responses to intraperitoneal IL-33 injections in mice and further addressed the responsiveness of human mast cells to IL-33. Our data demonstrate that a large proportion of the IL-33R ϩ cells in the peritoneal cavity are c-Kit ϩ Fc⑀RI ϩ mast cells, and that IL-33 induces neutrophil influx in the peritoneum of mice through a mast cell-dependent mechanism partly dependent on mast cell-derived TNF. For personal use only. on May 11, 2018. by guest www.bloodjournal.org From Methods ...

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“…The response activated the NF-B inflammatory pathway that in turn stimulated IL-8 secretion (6,(17)(18)(19)(20). To explore the importance of NOD1 in the proinflammatory signaling pathway activated by PepT1-mediated Tri-DAP transport (21), we down-regulated NOD1 expression using an siRNA approach.…”

Section: Nod1 Expression Is Essential For Intestinal Inflammationmentioning

confidence: 99%

“…Tri-DAP Interacts Directly with NOD1 Protein-Tri-DAP is known to be a natural ligand of NOD1 (6,17,18,28,29). However, the direct interaction between Tri-DAP and NOD1 has not been studied, and the binding constant of the reaction remains unknown.…”

Section: Volume 286 • Number 35 • September 2 2011mentioning

confidence: 99%

l-Ala-γ-d-Glu-meso-diaminopimelic Acid (DAP) Interacts Directly with Leucine-rich Region Domain of Nucleotide-binding Oligomerization Domain 1, Increasing Phosphorylation Activity of Receptor-interacting Serine/Threonine-protein Kinase 2 and Its Interaction with Nucleotide-binding Oligomerization Domain 1

Laroui

Yan

Narui

et al. 2011

Journal of Biological Chemistry

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Commensal bacteria that colonize the human colon produce significant amounts of di/tripeptides. We were the first to report that PepT1 transports the small formylated bacterial peptide (fMLP) (1, 2). In the interval since that time, we have shown that other bacterial peptides, such as MDP 3 and Tri-DAP, may also be transported by hPepT1 (3, 4). Small bacterial peptides occur at substantially lower levels in the small intestine compared with the colon in line with the reduced numbers of prokaryotes present in the small intestine of humans. Interestingly, hPepT1 expression is normally restricted to the small intestine, a site in which the levels of small bacterial peptides are low, reflecting the sparse bacterial load of this tissue relative to that of the colon. Thus, the profile of hPepT1 expression along the normal human digestive tract is such that access of small bacterial peptides to hPepT1 minimizes intracellular uptake of these peptides. This normal expression pattern becomes altered in patients with chronic ulcerative colitis or Crohn disease in whom expression of hPepT1 occurs in the colon. The transporter will consequently mediate the intracellular accumulation of small prokaryotic materials. We and others have shown that such accumulation of bacterial products (including

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Human Cord Blood-Derived Mast Cells Are Activated by the Nod1 Agonist M-TriDAP to Release Pro-Inflammatory Cytokines and Chemokines

Cited by 48 publications

References 84 publications

Activation of Nod1 Signaling Induces Fetal Growth Restriction and Death through Fetal and Maternal Vasculopathy

Activation of Nod1 Signaling Induces Fetal Growth Restriction and Death through Fetal and Maternal Vasculopathy

Intraperitoneal influx of neutrophils in response to IL-33 is mast cell–dependent

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