IL-18 induces a marked gene expression profile change and increased Ccl1 (I-309) production in mouse mucosal mast cell homologs

Wiener, Zoltán; Pócza, Péter; Rácz, Melinda; Nagy, György; Tölgyesi, Gergely; Molnár, Viktor; Jaeger, Judit; Buzás, Edit I.; Görbe, Éva; Papp, Zoltán; Rigó, János; Falus, András

doi:10.1093/intimm/dxn115

Cited by 19 publications

(11 citation statements)

References 43 publications

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“…The differences we have observed between CTMCs and MMCs/BMMCs are in keeping with several previous studies showing significant differences between these MC subsets, including differences in TLR expression (49), in responsiveness to IL-18 (which induces BMMCs/MMCs, but not CTMCs to secrete the chemokine, Ccll, to recruit Th2 cells) (58), in expression of STAT4 (in CTMCs) and STAT6 (in MMCs/BMMCs) (59) and in TLR-induced cytokines and chemokines (higher with CTMCs) (25). Differences have also been reported in IgE plus Ag-induced survival, with survival being more pronounced with CTMCs (60), and this may explain why IgE is a more potent survival enhancer of CTMCs than MMCs (Fig.…”

Section: Discussionsupporting

confidence: 92%

The Role of SHIP in the Development and Activation of Mouse Mucosal and Connective Tissue Mast Cells

Rüschmann

Antignano

Lam

et al. 2012

The Journal of Immunology

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Although SHIP is a well-established suppressor of IgE plus Ag-induced degranulation and cytokine production in bone marrow-derived mast cells (BMMCs), little is known about its role in connective tissue (CTMCs) or mucosal (MMCs) mast cells. In this study, we compared SHIP’s role in the development as well as the IgE plus Ag and TLR-induced activation of CTMCs, MMCs, and BMMCs and found that SHIP delays the maturation of all three mast cell subsets and, surprisingly, that it is a positive regulator of IgE-induced BMMC survival. We also found that SHIP represses IgE plus Ag-induced degranulation of all three mast cell subsets and that TLR agonists do not trigger their degranulation, whether SHIP is present or not, nor do they enhance IgE plus Ag-induced degranulation. In terms of cytokine production, we found that in MMCs and BMMCs, which are poor producers of TLR-induced cytokines, SHIP is a potent negative regulator of IgE plus Ag-induced IL-6 and TNF-α production. Surprisingly, however, in splenic or peritoneal derived CTMCs, which are poor producers of IgE plus Ag-induced cytokines, SHIP is a potent positive regulator of TLR-induced cytokine production. Lastly, cell signaling and cytokine production studies with and without LY294002, wortmannin, and PI3Kα inhibitor-2, as well as with PI3K p85α−/− BMMCs and CTMCs, are consistent with SHIP positively regulating TLR-induced cytokine production via an adaptor-mediated pathway while negatively regulating IgE plus Ag-induced cytokine production by repressing the PI3K pathway.

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Section: Discussionsupporting

confidence: 92%

The Role of SHIP in the Development and Activation of Mouse Mucosal and Connective Tissue Mast Cells

Rüschmann

Antignano

Lam

et al. 2012

The Journal of Immunology

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“…These genes have previously been described to be expressed by immune cells (Borregaard et al, 2007;Wiener et al, 2008;Yang et al, 2010). LCN2 and S100A9 displayed an increased expression in immune-cells isolated from RAC1 ko epidermis, but the levels of expression were much lower than in keratinocytes (Fig.…”

Section: Increased Activation But No Increased Numbers Of Immune Cellmentioning

confidence: 78%

RAC1 in keratinocytes regulates crosstalk to immune cells by Arp2/3 dependent control of STAT1

Pedersen

Wang

Stanley

et al. 2012

Journal of Cell Science

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SummaryCrosstalk between keratinocytes and immune cells is crucial for the immunological barrier function of the skin, and aberrant crosstalk contributes to inflammatory skin diseases. Using mice with a keratinocyte-restricted deletion of the RAC1 gene we found that RAC1 in keratinocytes plays an important role in modulating the interferon (IFN) response in skin. These RAC1 mutant mice showed increased sensitivity in an irritant contact dermatitis model, abnormal keratinocyte differentiation, and increased expression of immune response genes including the IFN signal transducer STAT1. Loss of RAC1 in keratinocytes decreased actin polymerization in vivo and in vitro and caused Arp2/3-dependent expression of STAT1, increased interferon sensitivity and upregulation of aberrant keratinocyte differentiation markers. This can be inhibited by the AP-1 inhibitor tanshinone IIA. Loss of RAC1 makes keratinocytes hypersensitive to inflammatory stimuli both in vitro and in vivo, suggesting a major role for RAC1 in regulating the crosstalk between the epidermis and the immune system.

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“…IL‐18 can stimulate mast cells, T cells, and basophils to secrete Th2 cytokines, such as IL‐13 and IL‐4. IL‐18 can also enhance Th2 and Th1 cell‐mediated immune responses . Thus, NLRP3 is an important PRR within the cytoplasm.…”

Section: Nlrp3 Inflammasomementioning

confidence: 94%

NLRP3 inflammasome: A likely target for the treatment of allergic diseases

Xiao

2018

Clin Experimental Allergy

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Allergic diseases, such as asthma, rhinitis, dermatitis, conjunctivitis, and anaphylaxis, have recently become a global public health concern. According to previous studies, the NLRP3 inflammasome is a multi-protein complex known to be associated with many inflammatory conditions. In response to allergens or allergen/damage-associated molecular signals, NLRP3 changes its conformation to allow the assembly of the NLRP3 inflammasome complex and activates caspase-1, which is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines IL-1β and IL-18. Subsequently, active caspase-1 cleaves pro-IL-1 and pro-IL-18. Recently, accumulating human and mouse experimental evidence has demonstrated that the NLRP3 inflammasome, IL-1β, and IL-18 are critically involved in the development of allergic diseases. Furthermore, the application of specific NLRP3 inflammasome inhibitors has been demonstrated in animal models. Therefore, these inhibitors may represent potential therapeutic methods for the management of clinical allergic disorders. This review summarizes findings related to the NLRP3 inflammasome and its related factors and concludes that specific NLRP3 inflammasome inhibitors may be potential therapeutic agents for allergic diseases.

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IL-18 induces a marked gene expression profile change and increased Ccl1 (I-309) production in mouse mucosal mast cell homologs

Cited by 19 publications

References 43 publications

The Role of SHIP in the Development and Activation of Mouse Mucosal and Connective Tissue Mast Cells

The Role of SHIP in the Development and Activation of Mouse Mucosal and Connective Tissue Mast Cells

RAC1 in keratinocytes regulates crosstalk to immune cells by Arp2/3 dependent control of STAT1

NLRP3 inflammasome: A likely target for the treatment of allergic diseases

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