Wounds that heal and wounds that don’t − The role of the IL-33/ST2 pathway in tissue repair and tumorigenesis

Millar, Neal L.; O'Donnell, Charlotte; McInnes, Iain B.; Brint, Elizabeth

doi:10.1016/j.semcdb.2016.08.007

Cited by 35 publications

(32 citation statements)

References 110 publications

(98 reference statements)

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“…It was found that interaction between H. pylori-derived RpL1aa 2-20 peptide (Hp 2-20) and cellular formyl peptide receptors (FPRs) induces cell migration and proliferation, as well as the expression of vascular endothelial growth factor (VEGF), which is involved in tissue regeneration [56]. Millar et al, showed that the binding of IL-33 with its secretory receptor (ST2) is necessary for initiation of tissue healing [38]. It has also been suggested that IL-33 is involved in tissue regeneration by activating group 2 innate lymphoid cell (ILC2) to deliver amphiregulin, a protein that is essential for epidermal growth, cell survival and proliferation [57].…”

Section: Pro-regenerative Activity Of Il-33 In the Cell Cultures Expomentioning

confidence: 99%

“…IL-33 is a newly described member of the IL-1 family of cytokines that is a DAMP and it is produced by cells under physiological conditions and potentially during several diseases. A summary of major IL-33 activities is presented in Table 1 [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]. DAMP signals the innate immune cells in response to stress or cell membrane disruption [33,34] Transcription factor regulates the gene expression [35][36][37][38] Cytokine signals the immune cells via ST2 receptor to eliminate infection and manage tissue injury (proregenerative activity) [39][40][41][42] modulates the T helper 2 (Th2) lymphocytes as well as Th1 and regulatory lymphocytes [43][44][45] upregulates the inflammatory response to bacterial LPS [42] potentially is involved in the development of disease due to maintenance of chronic inflammation [38,[44][45][46][47][48][49][50][51] DAMP (damage-associated molecular pattern); LPS (lipopolysaccharide); ST2 (secretory receptor, an interleukin (IL)-1 receptor family member); Th (T helper lymphocytes).…”

Section: Introductionmentioning

confidence: 99%

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Proregenerative Activity of IL-33 in Gastric Tissue Cells Undergoing Helicobacter Pylori-Induced Apoptosis

Gonciarz

Krupa

Chmiela

2020

IJMS

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Interleukin (IL)-33 is a proinflammatory mediator that alerts the host immune system to disorders in tissue homeostasis. Aim. To understand the role of IL-33 in modulating gastric tissue cell growth affected by Helicobacter pylori (H. pylori). Methods. IL-33 production in guinea pigs (Caviae porcellus) experimentally infected with H. pylori was evaluated by ELISA or immunohistochemical staining. The proregenerative activity of IL-33 was evaluated using gastric epithelial cells and fibroblasts that were naive or transfected with IL-33 siRNA exposed to H. pylori glycine acid extract antigenic complex (GE), as well as by measuring cell migration, proliferation, metabolic activity and apoptosis. Animals infected by H. pylori responded with increased production of IL-33. Also, cells treated in vitro with GE released more IL-33 than cells that were unstimulated. Silencing IL-33 in cells resulted in downregulation of metabolic activity, adhesion, migration and proliferation, especially after treatment with H. pylori GE, as well as upregulation of cells apoptosis associated with caspase 3 increase and Bcl-xL decrease, suggesting proregenerative activity of IL-33. Interestingly, upregulation of cell proliferation by IL-33 was Erk independent. Our results indicate that IL-33 may protect gastric tissue from loss of homeostasis caused by deleterious effects of H. pylori components and the inflammatory response developed during infection.

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Section: Pro-regenerative Activity Of Il-33 In the Cell Cultures Expomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proregenerative Activity of IL-33 in Gastric Tissue Cells Undergoing Helicobacter Pylori-Induced Apoptosis

Gonciarz

Krupa

Chmiela

2020

IJMS

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“…IL-33 correlated with the expression kinetics of the anti-apoptotic gene B-cell lymphoma 2 (Bcl-2), which is in agreement with its anti-apoptotic role ( 58 ). Thereafter, multiple experimental studies have also illustrated that IL-33 attenuates cardiac fibrosis induced by the increased cardiovascular load, showing that IL-33 directly inhibits pro-fibrotic activities of cardiac fibroblasts ( 58 , 59 , 137 ). Treatment of rat cardiac fibroblasts with IL-33 was also found to impair the migratory activity of fibroblasts or their precursors into the stressed myocardium ( 57 , 138 ).…”

Section: Il-33/st2 Axis In Heart Fibrosismentioning

confidence: 99%

IL-33/ST2 Axis in Organ Fibrosis

2018

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Interleukin 33 (IL-33) is highly expressed in barrier sites, acting via the suppression of tumorigenicity 2 receptor (ST2). IL-33/ST2 axis has long been known to play a pivotal role in immunity and cell homeostasis by promoting wound healing and tissue repair. However, it is also involved in the loss of balance between extensive inflammation and tissue regeneration lead to remodeling, the hallmark of fibrosis. The aim of the current review is to critically evaluate the available evidence regarding the role of the IL-33/ST2 axis in organ fibrosis. The role of the axis in tissue remodeling is better understood considering its crucial role reported in organ development and regeneration. Generally, the IL-33/ST2 signaling pathway has mainly anti-inflammatory/anti-proliferative effects; however, chronic tissue injury is responsible for pro-fibrogenetic responses. Regarding pulmonary fibrosis mature IL-33 enhances pro-fibrogenic type 2 cytokine production in an ST2- and macrophage-dependent manner, while full-length IL-33 is also implicated in the pulmonary fibrotic process in an ST2-independent, Th2-independent fashion. In liver fibrosis, evidence indicate that when acute and massive liver damage occurs, the release of IL-33 might act as an activator of tissue-protective mechanisms, while in cases of chronic injury IL-33 plays the role of a hepatic fibrotic factor. IL-33 signaling has also been involved in the pathogenesis of acute and chronic pancreatitis. Moreover, IL-33 could be used as an early marker for ulcer-associated activated fibroblasts and myofibroblast trans-differentiation; thus one cannot rule out its potential role in inflammatory bowel disease-associated fibrosis. Similarly, the upregulation of the IL-33/ST2 axismay contribute to tubular cell injury and fibrosis via epithelial to mesenchymal transition (EMT) of various cell types in the kidneys. Of note, IL-33 exerts a cardioprotective role via ST2 signaling, while soluble ST2 has been demonstrated as a marker of myocardial fibrosis. Finally, IL-33 is a crucial cytokine in skin pathology responsible for abnormal fibroblast proliferation, leukocyte infiltration and morphologic differentiation of human endothelial cells. Overall, emerging data support a novel contribution of the IL-33/ST2 pathway in tissue fibrosis and highlight the significant role of the Th2 pattern of immune response in the pathophysiology of organ fibrosis.

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“…As a nuclear factor, IL-33 binds to chromatin to repress the expression of inflammatory responses. As a cytokine, IL-33 is secreted into extracellular space in response to cell damage or mechanical injury [ 44 ]. IL-33 can then bind to the ST2L receptor, via its C-terminal IL-1 like cytokine domain, inducing a conformational change that results in recruitment of IL-1RAcP to form a heterodimeric receptor complex on the cell membrane [ 23 ].…”

Section: The Il-33/st2 Signaling Pathwaymentioning

confidence: 99%

The Role of IL-33/ST2 Pathway in Tumorigenesis

Larsen

Minaya

Vaish

et al. 2018

IJMS

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Cancer is initiated by mutations in critical regulatory genes; however, its progression to malignancy is aided by non-neoplastic cells and molecules that create a permissive environment known as the tumor stroma or microenvironment (TME). Interleukin 33 (IL-33) is a dual function cytokine that also acts as a nuclear factor. IL-33 typically resides in the nucleus of the cells where it is expressed. However, upon tissue damage, necrosis, or injury, it is quickly released into extracellular space where it binds to its cognate receptor suppression of tumorigenicity 2 (ST2)L found on the membrane of target cells to potently activate a T Helper 2 (Th2) immune response, thus, it is classified as an alarmin. While its role in immunity and immune-related disorders has been extensively studied, its role in tumorigenesis is only beginning to be elucidated and has revealed opposing roles in tumor development. The IL-33/ST2 axis is emerging as a potent modulator of the TME. By recruiting a cohort of immune cells, it can remodel the TME to promote malignancy or impose tumor regression. Here, we review its multiple functions in various cancers to better understand its potential as a therapeutic target to block tumor progression or as adjuvant therapy to enhance the efficacy of anticancer immunotherapies.

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Wounds that heal and wounds that don’t − The role of the IL-33/ST2 pathway in tissue repair and tumorigenesis

Cited by 35 publications

References 110 publications

Proregenerative Activity of IL-33 in Gastric Tissue Cells Undergoing Helicobacter Pylori-Induced Apoptosis

Proregenerative Activity of IL-33 in Gastric Tissue Cells Undergoing Helicobacter Pylori-Induced Apoptosis

IL-33/ST2 Axis in Organ Fibrosis

The Role of IL-33/ST2 Pathway in Tumorigenesis

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