Critical role of inflammatory mast cell in fibrosis: Potential therapeutic effect of <scp>IL</scp>‐37

Conti, Pio; Caraffa, Auro; Mastrangelo, Filiberto; Tettamanti, L; Ronconi, Gianpaolo; Frydas, Ilias; Kritas, S K; Theoharides, Theoharis C.

doi:10.1111/cpr.12475

Cited by 40 publications

(26 citation statements)

References 57 publications

(139 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, as described above, IL-37 plays an important anti-inflammatory and immunomodulatory capacity in a variety of inflammatory and autoimmune diseases. In addition, IL-37 in vivo could inhibit NLRP3 activation also be mentioned in colitis and LPS-induced disease [19,22,[35][36][37]. In recent study, Rudloff et al reported that IL-37 significantly suppress inflammasome activity in vivo to ameliorate inflammasome-driven diseases, which could corroborate our study results to some extent [38].…”

Section: Discussionsupporting

confidence: 90%

“…Interleukin 37 (IL-37) is a novel cytokine that recently characterized a member in the IL-1 family, which plays a key role in limiting excessive and runaway inflammatory responses via suppressing both innate and adaptive immunity [19][20][21]. It has been demonstrated that a knockdown of endogenous IL-37 in human peripheral blood mononuclear cells, which results in increased production of several pro-inflammatory cytokines [22]. Human IL-37 transgenic mice are protected against metabolic syndrome, systemic inflammation reaction, DSS-induced colitis, and acute myocardial infarction.…”

Section: Irimentioning

confidence: 99%

See 1 more Smart Citation

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

Kong

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Ischemia reperfusion injury (IRI) is the major cause of intestinal damage in clinic. Although either mesenchymal stromal cells (MSCs) or interleukin 37 (IL-37) showed some beneficial roles to ameliorate IRI, their effects are limited. In this study, the protective effects of IL-37 gene-modified MSCs (IL-37-MSCs) for better prevention of intestinal IRI are investigated.Methods: Intestinal IRI model was established by occluding the superior mesenteric artery for 30min and then reperfusing for 72 hours in rats. Forty adult male SD rats were randomly divided into sham control, IL-37-MSC-treated, MSC-treated, recombinant IL-37 (rIL-37)-treated and untreated groups. Intestinal damage was assessed by H&E staining. The levels of gut barrier function factors (diamine oxidase and D-Lactate) and inflammation reactivity cytokine IL-1β were assayed by ELISA. The expressions of tissue damage-related NLRP3 inflammasome and relative proteins including clevead caspase-1, IL-1β and IL-18 were detected by western blot. As downstream of IL-1β and IL-18, the mRNA levels of proinflammatory mediators IL-6 and TNF-α were determined by qPCR. Data were analyzed by one-way analysis of variance among groups.Results: IL-37-MSCs were able to migrate to the damaged tissue and significantly inhibit intestinal IRI. As compared with MSCs or rIL-37 monotherapy group, IL-37-MSC treatment not only improved gut barrier function but also decreased local and systemic inflammation reactivity cytokine IL-1β level in IRI rats. In addition, tissue damage-related NLRP3 and relative proteins (cleaved caspase-1, IL-1β and 4 IL-18) were significantly decreased in IRI rats treated with IL-37-MSCs. Furthermore, IL-1β and IL-18 related proinflammatory mediators IL-6 and TNF-α mRNA expressions were markedly decreased following IL-37-MSC treatment.Conclusion: The results suggest that IL-37 gene modification significantly enhance the protective effects of MSCs against intestinal IRI. In addition, NLRP3-related signaling pathways could be associated with IL-37-MSC mediated protection.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Irimentioning

confidence: 99%

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

Kong

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Animal models of chronic skin inflammation highlight potential mast cell roles [127]. Whether in the skin or elsewhere, mast cells influence fibrosis [129,130]. In early scleroderma, there are increased numbers of mast cells in affected skin along with increased circulating plasma histamine [131].…”

Section: The Mast Cell As the Potential Common Denominatormentioning

confidence: 99%

Mast Cell Biology and Linkages for Non-clonal Mast Cell Activation and Autoimmune/Inflammatory Syndrome Induced by Adjuvants

Cimolai

2020

SN Compr. Clin. Med.

View full text Add to dashboard Cite

Non-clonal mast cell activation disorder (syndrome) (NC-MCAD) and autoimmune/inflammatory syndrome induced by adjuvants (ASIA) are complex syndromic and spectral clinical entities which have contemporaneously garnered considerable attention and rightfully so. NC-MCAD presents with a predominantly allergic profile, and causative clinical variables may or may not be identified. Manifest NC-MCAD illnesses can be complex and involve several organ systems. Such diversity may be in part explained by the ubiquity and plasticity of the mast cell. ASIA, due to its broad definition, continues to expand as a clinical entity, especially with the greater recognition of what might constitute adjuvancy. Such diversity has the potential to overly stretch the boundaries for scientific investigation. For both NC-MCAD and ASIA, the inciting molecular mechanisms require elucidation. Future research would benefit from greater precision for clinical diagnosis and risk factor identification, and the latter would be potentially facilitated by the discovery of reliable laboratory markers. Some patients with ASIA may present with clinical features that may be identified as NC-MCAD. This review examines the potential spectral nexus of NC-MCAD and ASIA and considers the role of the mast cell in such a possible interface.

show abstract

“…The soluble form of ST2 acts as a decoy receptor and captures IL-33 and does not signal; while the cell membrane-linked form has biological activity through the activation of MyD88/NF–κB in several immune cells including MCs. Following the specific binding of IL-33 to the ST2 plasma membrane receptor, NF-κB and MAPK are induced [ 79 ]. IL-33 is secreted by smooth muscle cells, endothelial cells, macrophages, dendritic cells, fibroblasts, epithelial cells, and keratinocytes, all implicated in pSS [ 80 ].…”

Section: Il-33mentioning

confidence: 99%

Advances in Mast Cell Activation by IL-1 and IL-33 in Sjögren’s Syndrome: Promising Inhibitory Effect of IL-37

Conti

Stellin

Caraffa

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Sjögren’s syndrome (SS) is a chronic autoimmune inflammatory disease that affects primarily older women and is characterized by irreversible damage of the exocrine glands, including tear (xerophthalmia) and salivary glands (xerostomia). Secretory glands lose their functionality due to the infiltration of immune cells, which produce cytokines and cause inflammation. Primary SS is characterized by dry syndrome with or without systemic commitment in the absence of other pathologies. Secondary SS is accompanied by other autoimmune diseases with high activation of B lymphocytes and the production of autoantibodies, including the rheumatoid factor. Other cells, such as CD4+ T cells and mast cells (MCs), participate in SS inflammation. MCs are ubiquitous, but are primarily located close to blood vessels and nerves and can be activated early in autoimmune diseases to express a wide variety of cytokines and chemokines. In the SS acute phase, MCs react by generating chemical mediators of inflammation, tumor necrosis factor (TNF), and other pro-inflammatory cytokines such as interleukin (IL)-1 and IL-33. IL-33 is the specific ligand for ST2 capable of inducing some adaptive immunity TH2 cytokines but also has pro-inflammatory properties. IL-33 causes impressive pathological changes and inflammatory cell infiltration. IL-1 family members can have paracrine and autocrine effects by exacerbating autoimmune inflammation. IL-37 is an IL-1 family cytokine that binds IL-18Rα receptor and/or Toll-like Receptor (TLR)4, exerting an anti-inflammatory action. IL-37 is a natural inhibitor of innate and acquired immunity, and the level is abnormal in patients with autoimmune disorders. After TLR ligand activation, IL-37 mRNA is generated in the cytoplasm, with the production of pro-IL-37 and later mature IL-37 caspase-1 mediated; both precursor and mature IL-37 are biologically active. Here, we discuss, for the first time, the current knowledge of IL-37 in autoimmune disease SS and propose a new therapeutic role.

show abstract

Critical role of inflammatory mast cell in fibrosis: Potential therapeutic effect of IL‐37

Abstract: This review summarizes current knowledge on the role of MC in inflammation and tissue/organ fibrosis, with a focus on the therapeutic potential of IL-37-targeting cytokines.

Cited by 40 publications

References 57 publications

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

Mast Cell Biology and Linkages for Non-clonal Mast Cell Activation and Autoimmune/Inflammatory Syndrome Induced by Adjuvants

Advances in Mast Cell Activation by IL-1 and IL-33 in Sjögren’s Syndrome: Promising Inhibitory Effect of IL-37

Contact Info

Product

Resources

About