IL-33 and IL-4 impair barrier functions of human vascular endothelium via different mechanisms

Chałubiński, Maciej; Wojdan, Katarzyna; Luczak, Emilia; Gorzelak, Paulina; Borowiec, Maciej; Gajewski, Adrian; Rudnicka, Karolina; Chmiela, Magdalena; Broncel, Marlena

doi:10.1016/j.vph.2015.07.012

Cited by 39 publications

(29 citation statements)

References 28 publications

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“…We and others have demonstrated that symptoms of food-induced anaphylaxis in mice are dependent on IgE-MCs and histamine type I receptor signaling and that the severity of the reaction positively correlates with an increase in hemoconcentration (an indication for fluid extravasation and hypovolemic shock) 23–26 . In vitro experimental evidence suggests that IL-4 modulates VE barrier properties 27–29 and we have demonstrated that IL-4 can interact with vasoactive mediators to increase hemoconcentration and the severity of anaphylaxis 30, 31 . However, the cellular target of these IL-4-mediated effects and the underlying IL-4Rα-dependent signaling processes involved in the amplification of histamine-induced VE barrier dysfunction and fluid extravasation in IgE-mediated reactions is not yet fully understood.…”

Section: Introductionmentioning

confidence: 73%

The vascular endothelial specific IL-4 receptor alpha–ABL1 kinase signaling axis regulates the severity of IgE-mediated anaphylactic reactions

Yamani

Waggoner

et al. 2018

Journal of Allergy and Clinical Immunology

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Background Severe IgE-mediated, food-induced anaphylactic reactions are characterized by pulmonary venous vasodilatation and fluid extravasation, which is thought to lead to the life-threatening anaphylactic phenotype. The underlying immunological and cellular processes involved in driving fluid extravasation and the severe anaphylactic phenotype are not fully elucidated. Objective To define the interaction and requirement of IL-4 and vascular endothelial (VE) IL-4Rα chain signaling in histamine-ABL1–mediated VE dysfunction and fluid extravasation in the severity of IgE-mediated anaphylactic reactions in mice. Methods Mice deficient in VE IL-4Rα and models of passive and active oral antigen– and IgE-induced anaphylaxis were employed to define the requirements of VE IL-4Rα and ABL1 pathway in severe anaphylactic reactions. Human VE cell line (EA.hy926 cells) and pharmacologic (imatinib) and genetic approaches (shRNA knockdown of IL4RA and ABL1) were used to define the requirement of this pathway in VE barrier dysfunction. Results IL-4 exacerbation of histamine-induced hypovolemic shock in mice was dependent on VE expression of the IL-4Rα. IL-4 and histamine induced ABL1 activation in human VE cells and VE barrier dysfunction was ABL1 dependent. Development of severe IgE-mediated hypovolemia and shock required VE-restricted ABL1 expression. Treatment of mice with a history of food-induced anaphylaxis with the ABL kinase inhibitor imatinib protected the mice from developing severe IgE-mediated anaphylaxis. Conclusion IL-4 amplifies IgE- and histamine-induced VE dysfunction, fluid extravasation, and severity of anaphylaxis via a VE IL-4Rα-ABL1–dependent mechanism. These studies implicate an important contribution by the VE compartment in the severity of anaphylaxis and identify a new pathway for therapeutic intervention of IgE-mediated reactions.

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Section: Introductionmentioning

confidence: 73%

The vascular endothelial specific IL-4 receptor alpha–ABL1 kinase signaling axis regulates the severity of IgE-mediated anaphylactic reactions

Yamani

Waggoner

et al. 2018

Journal of Allergy and Clinical Immunology

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“…In recent years, IL-33 has been the focus of interest to have a relationship with endothelial functions. In a study performed by Chalubinski et al, they showed that IL-4 and IL-33 destroyed human microvascular endothelium in different ways [45]. IL-33 and IL-4 caused the endothelial integrity to decrease and the permeability to increase.…”

Section: Discussionmentioning

confidence: 99%

“…IL-33 and IL-4 caused the endothelial integrity to decrease and the permeability to increase. When IL-33 and IL-4 were added together, they caused the endothelial integrity to decrease by two-fold than when they were administered separately [45]. Down-regulation of occluding and VE-cadherin mRNA expression accompanies this effect.…”

Section: Discussionmentioning

confidence: 99%

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IL-33 and ST2 levels in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events, and survival

et al. 2017

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ObjectiveIncreased inflammation, associated with the increase in chronic kidney disease (CKD) stage, has a very important influence in vascular injury and cardiovascular diseases. In this study, we aimed to investigate the levels of IL-33 and ST2 in the different stages of CKD and to determine their effect on vascular damage and cardiovascular events (CVE).MethodsThis was an observational cohort study in which serum IL-33 and ST2 were obtained from 238 CKD (stages 1–5) patients. We examined the changes in IL-33/ST2 levels in CKD patients, as well as the association with a surrogate of endothelial dysfunction. Fatal and non-fatal CVE were recorded for a mean of 24 months. We also performed a COX regression analysis to determine the association of IL-33/ST2 levels with CVE and survival.ResultsIL-33 and ST2 levels were significantly increased and estimated glomerular filtration rates (eGFR) were decreased. Flow-mediated dilatation (FMD) was significantly decreased from stage 1 to stage 5 CKD. IL-33 and ST2 levels were associated with FMD, and ST2 was a predictor. Multivariate Cox analysis showed that the presence of diabetes mellitus, smoking, and proteinuria and haemoglobin, Hs-CRP, IL-33, and ST2 were associated with the risk of CVE. Kaplan-Meier survival curves showed that patients with IL-33 and ST2 levels below the median value (IL-33 = 132.6 ng/L, ST2 = 382.9 pg/mL) had a higher cumulative survival compared with patients who had IL-33 and ST2 levels above the median value (log-rank test, p = 0.000).ConclusionThis is the first study that demonstrates that serum IL-33 and ST2 are associated with vascular injury, cardiovascular events, and survival in CKD patients.

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“…In the gastric epithelium, colonized by pathogenic microorganisms, including H. pylori , probably IL-33 acting as an alarming molecule can induce the signalling beneficial for tissue recovery due to a short-term increase in endothelial permeability. However, under some circumstances it may cause the aggravation of inflammation and tissue dysfunction by attracting Th2 lymphocytes, promotion of cell apoptosis and maintenance of tissue dysfunction[95]. In vivo , during H. pylori infection different environmental conditions ( e.g ., stress, nutrients, pH), time of the cell exposure to bacterial antigens and their concentration may also determine the fate of different cell types.…”

Section: Discussionmentioning

confidence: 99%

Impact ofHelicobacter pylorion the healing process of the gastric barrier

Mnich¹,

Kowalewicz-Kulbat²,

Sicińska³

et al. 2016

WJG

Self Cite

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AIMTo determine the impact of selected well defined Helicobacter pylori (H. pylori) antigens on gastric barrier cell turnover.METHODSIn this study, using two cellular models of gastric epithelial cells and fibroblasts, we have focused on exploring the effects of well defined H. pylori soluble components such as glycine acid extract antigenic complex (GE), subunit A of urease (UreA), cytotoxin associated gene A protein (CagA) and lipopolysaccharide (LPS) on cell turnover by comparing the wound healing capacity of the cells in terms of their proliferative and metabolic activity as well as cell cycle distribution. Toxic effects of H. pylori components have been assessed in an association with damage to cell nuclei and inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation.RESULTSWe showed that H. pylori GE, CagA and UreA promoted regeneration of epithelial cells and fibroblasts, which is necessary for effective tissue healing. However, in vivo increased proliferative activity of these cells may constitute an increased risk of gastric neoplasia. In contrast, H. pylori LPS showed a dose-dependent influence on the process of wound healing. At a low concentration (1 ng/mL) H. pylori LPS accelerated of healing epithelial cells, which was linked to significantly enhanced cell proliferation and MTT reduction as well as lack of alterations in cell cycle and downregulation of epidermal growth factor (EGF) production as well as cell nuclei destruction. By comparison, H. pylori LPS at a high concentration (25 ng/mL) inhibited the process of wound repair, which was related to diminished proliferative activity of the cells, cell cycle arrest, destruction of cell nuclei and downregulation of the EGF/STAT3 signalling pathway.CONCLUSIONIn vivo H. pylori LPS driven effects might lead to the maintenance of chronic inflammatory response and pathological disorders on the level of the gastric mucosal barrier.

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IL-33 and IL-4 impair barrier functions of human vascular endothelium via different mechanisms

Cited by 39 publications

References 28 publications

The vascular endothelial specific IL-4 receptor alpha–ABL1 kinase signaling axis regulates the severity of IgE-mediated anaphylactic reactions

The vascular endothelial specific IL-4 receptor alpha–ABL1 kinase signaling axis regulates the severity of IgE-mediated anaphylactic reactions

IL-33 and ST2 levels in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events, and survival

Impact ofHelicobacter pylorion the healing process of the gastric barrier

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