Signal transduction and chemotaxis in mast cells

Dráber, Petr; Hálová, Ivana; Polakovičová, Iva; Kawakami, Toshiaki

doi:10.1016/j.ejphar.2015.02.057

Cited by 60 publications

(48 citation statements)

References 190 publications

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“…Multivalent antigen crosslinks IgE‐FcεRI complexes on the cell surface and triggers a series of activation events. The process starts by engagement of the Src family protein tyrosine kinases LYN and FYN . LYN phosphorylates ITAM motives of the adjacent β and γ chains, as well as the kinase SYK that is recruited to the phosphorylated FcεRI γ subunit.…”

Section: Fcεri Signalingmentioning

confidence: 99%

“…The process starts by engagement of the Src family protein tyrosine kinases LYN and FYN. [11][12][13][14] LYN phosphorylates ITAM motives of the adjacent β and γ chains, as well as the kinase SYK that is recruited to the phosphorylated FcεRI γ subunit. How LYN initiates the signaling cascade has not been completely elucidated and several models exist.…”

Section: Fcεri Signalingmentioning

confidence: 99%

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Changing the threshold—Signals and mechanisms of mast cell priming

Hálová

Rönnberg

Dráberová

et al. 2018

Immunological Reviews

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Mast cells play a key role in allergy and other inflammatory diseases involving engagement of multivalent antigen with IgE bound to high-affinity IgE receptors (FcεRIs). Aggregation of FcεRIs on mast cells initiates a cascade of signaling events that eventually lead to degranulation, secretion of leukotrienes and prostaglandins, and cytokine and chemokine production contributing to the inflammatory response. Exposure to pro-inflammatory cytokines, chemokines, bacterial and viral products, as well as some other biological products and drugs, induces mast cell transition from the basal state into a primed one, which leads to enhanced response to IgE-antigen complexes. Mast cell priming changes the threshold for antigen-mediated activation by various mechanisms, depending on the priming agent used, which alone usually do not induce mast cell degranulation. In this review, we describe the priming processes induced in mast cells by various cytokines (stem cell factor, interleukins-4, -6 and -33), chemokines, other agents acting through G protein-coupled receptors (adenosine, prostaglandin E , sphingosine-1-phosphate, and β-2-adrenergic receptor agonists), toll-like receptors, and various drugs affecting the cytoskeleton. We will review the current knowledge about the molecular mechanisms behind priming of mast cells leading to degranulation and cytokine production and discuss the biological effects of mast cell priming induced by several cytokines.

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Section: Fcεri Signalingmentioning

confidence: 99%

Section: Fcεri Signalingmentioning

confidence: 99%

Changing the threshold—Signals and mechanisms of mast cell priming

Hálová

Rönnberg

Dráberová

et al. 2018

Immunological Reviews

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“…As a chemotactic factor of MCs, SCF may promote the regeneration of MC from CD34 + progenitor cells, MC survival and adhesion to the extracellular matrix (25). Importantly, histamine levels decline substantially when the SCF/c-Kit system is repressed and the SCF/c-Kit axis has been repeatedly identified as one of the most promising targets for controlling MC inflammation (26,45). Indeed, evidence suggests that SCF inhibition potentially lowers visceral sensitivity via modulation of the MC compartment (46).…”

Section: Regulation Of the Scf/c-kit System Affects The Function Of Amentioning

confidence: 99%

Role of stem cell growth factor/c-Kit in the pathogenesis of irritable bowel syndrome

Chai

Huang

Tang

et al. 2017

Experimental and Therapeutic Medicine

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Irritable bowel syndrome (IBS) is a functional bowel disease with a complicated etiopathogenesis, often characterized by gastrointestinal motility disorder and high visceral sensitivity. IBS is a comprehensive multi-systemic disorder, with the interaction of multiple factors, such as mental stress, intestinal function and flora, heredity, resulting in the disease. The existence of a common mechanism underlying the aforementioned factors is currently unknown. The lack of therapies that comprehensively address the disease symptoms, including abdominal pain and diarrhea, is a limitation of current IBS management. The current review has explored the role of the SCF/c-Kit receptor/ligand system in IBS. The SCF/c-Kit system constitutes a classical ligand/receptor tyrosine kinase signaling system that mediates inflammation and smooth muscle contraction. Additionally, it provides trophic support to neural crest-derived cell types, including the enteric nervous system and mast cells. The regulation of SCF/c-Kit on the interstitial cells of Cajal (ICC) suggest that it may play a key role in the aberrant intestinal dynamics and high visceral sensitivity observed in IBS. The role of the SCF/c-Kit system in intestinal motility, inflammation and nerve growth has been reported. From the available biomedical evidence on the pathogenesis of IBS, it has been concluded that the SCF-c-Kit system is a potential therapeutic target for rational drug design in the treatment of IBS.

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“…While the biology of these diseases is complex, all share a central role for mast cell activation as an initiator of symptoms. IgE-mediated mast cell activation elicits release of preformed mediators such as histamine and the production of arachidonic acid metabolites, cytokines, and chemokines that collectively increase vascular permeability, constrict airways, and recruit leukocytes to inflammatory sites (1–3). However, IgE-mediated responses are not exclusively responsible for allergic inflammation.…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 Suppresses IL-33–Induced Mast Cell Function

Ndaw

Abebayehu

Spence

et al. 2017

The Journal of Immunology

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TGFβ1 is involved in many pathological conditions, including autoimmune disorders, cancer, cardiovascular and allergic diseases. We have previously found that TGFβ1 can suppress IgE-mediated mast cell activation of human and mouse mast cells. IL-33 is a member of the IL-1 family capable of inducing mast cell responses and enhancing IgE-mediated activation. In this study, we investigated the effects of TGFβ on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGFβ −1, −2, or −3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13 and MCP-1, in a concentration-dependent manner. TGFβ1 inhibited IL-33-mediated Akt and ERK phosphorylation as well as NFκB- and AP-1-mediated transcription. These effects were functionally important, as TGFβ1 injection suppressed IL-33-induced systemic cytokines in vivo and inhibited IL-33-mediated cytokine release from human mast cells. TGFβ1 also suppressed the combined effects of IL-33 and IgE-mediated activation on mouse and human mast cells. The role of IL-33 in the pathogenesis of allergic diseases is incompletely understood. These findings, consistent with our previously reported effects of TGFβ1 on IgE-mediated activation, demonstrate that TGFβ1 can provide broad inhibitory signals to activated mast cells.

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Signal transduction and chemotaxis in mast cells

Cited by 60 publications

References 190 publications

Changing the threshold—Signals and mechanisms of mast cell priming

Changing the threshold—Signals and mechanisms of mast cell priming

Role of stem cell growth factor/c-Kit in the pathogenesis of irritable bowel syndrome

TGF-β1 Suppresses IL-33–Induced Mast Cell Function

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