scholarly journals Modulation of Mast Cell Toll-Like Receptor 3 Expression and Cytokines Release by Histamine

2018 ◽  
Vol 46 (6) ◽  
pp. 2401-2411 ◽  
Author(s):  
Guogang Xie ◽  
Feng Wang ◽  
Xia Peng ◽  
Yuting Liang ◽  
Haiwei Yang ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Cytokine Production ◽  
Inflammatory Cells ◽  
Mast Cell Activation ◽  
Toll Like Receptor ◽  
H1 Receptor ◽  
Mrna And Protein Expression ◽  
Tlr3 Mrna

Background/Aims: As a major inflammatory molecule released from mast cell activation, histamine has been reported to regulate TLRs expression and cytokine production in inflammatory cells present in the microenvironment. In this study, we determined the ability of histamine to modulate TLRs expression and cytokine production in mast cells. Methods: HMC-1 and P815 cells were exposed to various concentrations of histamine in the presence or absence of histamine antagonist for 2, 6 or 16 h. The effect of histamine on the expression of TLR3 protein and mRNA was analyzed by flow cytometry、 RT-PCR and immunofluorescent microscopy. Furthermore, we also examined the effect of histamine on the secretion of MCP-1 and IL-13 from mast cells by ELISA. Results: The amplification of TLR3 mRNA and protein expression in mast cells was observed after incubation with histamine, which was accompanied by increasing secretion of IL-13 and MCP-1 via H1 receptor. The signaling pathways of PI3K/ Akt and Erk1/2/MAPK contributed to these induction effects. Conclusion: These results demonstrate that histamine up-regulates the expression of TLR3 and secretion of IL-13 and MCP-1 in mast cells, thus identifying a new mechanism for the histamine inducing allergic response.

scholarly journals Resveratrol inhibits IL-33–mediated mast cell activation by targeting the MK2/3–PI3K/Akt axis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shotaro Nakajima ◽  
Kayoko Ishimaru ◽  
Anna Kobayashi ◽  
Guannan Yu ◽  
Yuki Nakamura ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Cytokine Production ◽  
Allergic Diseases ◽  
Mast Cell Activation ◽  
Akt Pathway ◽  
Mouse Lung ◽  
Mouse Bone Marrow ◽  
Interleukin 33

AbstractInterleukin-33 (IL-33)/ST2–mediated mast cell activation plays important roles in the pathophysiology of allergic diseases. Hence, pharmacologically targeting the IL-33/ST2 pathway in mast cells could help to treat such diseases. We found that resveratrol inhibits IL-33/ST2–mediated mast cell activation. Resveratrol suppressed IL-33–induced IL-6, IL-13, and TNF-α production in mouse bone marrow–derived mast cells (BMMCs), mouse fetal skin–derived mast cells, and human basophils. Resveratrol also attenuated cytokine expression induced by intranasal administration of IL-33 in mouse lung. IL-33–mediated cytokine production in mast cells requires activation of the NF-κB and MAPK p38–MAPK-activated protein kinase-2/3 (MK2/3)–PI3K/Akt pathway, and resveratrol clearly inhibited IL-33–induced activation of the MK2/3–PI3K/Akt pathway, but not the NF-κB pathway, without affecting p38 in BMMCs. Importantly, resveratrol inhibited the kinase activity of MK2, and an MK2/3 inhibitor recapitulated the suppressive effects of resveratrol. Resveratrol and an MK2/3 inhibitor also inhibited IgE-dependent degranulation and cytokine production in BMMCs, concomitant with suppression of the MK2/3–PI3K/Akt pathway. These findings indicate that resveratrol inhibits both IL-33/ST2–mediated and IgE-dependent mast cell activation principally by targeting the MK2/3–PI3K/Akt axis downstream of p38. Thus, resveratrol may have potential for the prevention and treatment of broad ranges of allergic diseases.

scholarly journals Tespa1 negatively regulates FcεRI-mediated signaling and the mast cell–mediated allergic response

2014 ◽  
Vol 211 (13) ◽  
pp. 2635-2649 ◽  
Author(s):  
Di Wang ◽  
Mingzhu Zheng ◽  
Yuanjun Qiu ◽  
Chuansheng Guo ◽  
Jian Ji ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Cytokine Production ◽  
Adaptor Protein ◽  
Mast Cell Activation ◽  
Allergic Reactions ◽  
Proinflammatory Cytokine Production ◽  
Increased Sensitivity ◽  
Ige Mediated

Antigen-mediated cross-linking of IgE on mast cells triggers a signaling cascade that results in their degranulation and proinflammatory cytokine production, which are key effectors in allergic reactions. We show that the activation of mast cells is negatively regulated by the newly identified adaptor protein Tespa1. Loss of Tespa1 in mouse mast cells led to hyper-responsiveness to stimulation via FcεRI. Mice lacking Tespa1 also displayed increased sensitivity to IgE-mediated allergic responses. The dysregulated signaling in KO mast cells was associated with increased activation of Grb2-PLC-γ1-SLP-76 signaling within the LAT1 (linker for activation of T cells family, member 1) signalosome versus the LAT2 signalosome. Collectively, these findings show that Tespa1 orchestrates mast cell activation by tuning the balance of LAT1 and LAT2 signalosome assembly.

scholarly journals Regulation of mast cell survival and function by tuberous sclerosis complex 1

Blood ◽  
2012 ◽  
Vol 119 (14) ◽  
pp. 3306-3314 ◽  
Author(s):  
Jinwook Shin ◽  
Hongjie Pan ◽  
Xiao-Ping Zhong
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Survival ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Cell Activation ◽  
Cytokine Production ◽  
Mast Cell Degranulation ◽  
Mtor Signaling ◽  
Mast Cell Activation

Abstract Mast cells play critical roles in allergic disorders and asthma. The importance of tuberous sclerosis complex 1/2-mammalian target of rapamycin (TSC1/2-mTOR) signaling in mast cells is unknown. Here, we report that TSC1 is a critical regulator for mTOR signaling in mast cells downstream of FcεRI and c-Kit, and differentially controls mast cell degranulation and cytokine production. TSC1-deficiency results in impaired mast cell degranulation, but enhanced cytokine production in vitro and in vivo after FcεRI engagement. Furthermore, TSC1 is critical for mast cell survival through multiple pathways of apoptosis including the down-regulation of p53, miR-34a, reactive oxygen species, and the up-regulation of Bcl-2. Together, these findings reveal that TSC1 is a critical regulator of mast cell activation and survival, suggesting the manipulation of the TSC1/2-mTOR pathway as a therapeutic strategy for mast cell-mediated diseases.

scholarly journals The Bcl10–Malt1 complex segregates FcεRI-mediated nuclear factor κB activation and cytokine production from mast cell degranulation

2006 ◽  
Vol 203 (2) ◽  
pp. 337-347 ◽  
Author(s):  
Stefanie Klemm ◽  
Jan Gutermuth ◽  
Lothar Hültner ◽  
Tim Sparwasser ◽  
Heidrun Behrendt ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Cytokine Production ◽  
De Novo ◽  
Late Phase ◽  
B Cell Lymphoma ◽  
Nuclear Factor Κb ◽  
Mast Cell Activation ◽  
Nuclear Factor

Mast cells are pivotal effector cells in IgE-mediated allergic inflammatory diseases. Central for mast cell activation are signals from the IgE receptor FcεRI, which induce cell degranulation with the release of preformed mediators and de novo synthesis of proinflammatory leukotrienes and cytokines. How these individual mast cell responses are differentially controlled is still unresolved. We identify B cell lymphoma 10 (Bcl10) and mucosa-associated lymphoid tissue 1 (Malt1) as novel key regulators of mast cell signaling. Mice deficient for either protein display severely impaired IgE-dependent late phase anaphylactic reactions. Mast cells from these animals neither activate nuclear factor κB (NF-κB) nor produce tumor necrosis factor α or interleukin 6 upon FcεRI ligation even though proximal signaling, degranulation, and leukotriene secretion are normal. Thus, Bcl10 and Malt1 are essential positive mediators of FcεRI-dependent mast cell activation that selectively uncouple NF-κB–induced proinflammatory cytokine production from degranulation and leukotriene synthesis.

scholarly journals Identification of 5-Hydroxymethylfurfural (5-HMF) as an Active Component Citrus Jabara That Suppresses FcεRI-Mediated Mast Cell Activation

2020 ◽  
Vol 21 (7) ◽  
pp. 2472 ◽  
Author(s):  
Ryota Uchida ◽  
Michiko Kato ◽  
Yuka Hattori ◽  
Hiroko Kikuchi ◽  
Emi Watanabe ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Active Component ◽  
Cell Activation ◽  
Cytokine Production ◽  
Citrus Fruit ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Active Components ◽  
Seasonal Allergies

Jabara (Citrus jabara Hort. ex Y. Tanaka) is a type of citrus fruit known for its beneficial effect against seasonal allergies. Jabara is rich in the antioxidant narirutin whose anti-allergy effect has been demonstrated. One of the disadvantages in consuming Jabara is its bitter flavor. Therefore, we fermented the fruit to reduce the bitterness and make Jabara easy to consume. Here, we examined whether fermentation alters the anti-allergic property of Jabara. Suppression of degranulation and cytokine production was observed in mast cells treated with fermented Jabara and the effect was dependent on the length of fermentation. We also showed that 5-hydroxymethylfurfural (5-HMF) increases as fermentation progresses and was identified as an active component of fermented Jabara, which inhibited mast cell degranulation. Mast cells treated with 5-HMF also exhibited reduced degranulation and cytokine production. In addition, we showed that the expression levels of phospho-PLCγ1 and phospho-ERK1/2 were markedly reduced upon FcεRI stimulation. These results indicate that 5-HMF is one of the active components of fermented Jabara that is involved in the inhibition of mast cell activation.

scholarly journals Brain mast cells link the immune system to anxiety-like behavior

2008 ◽  
Vol 105 (46) ◽  
pp. 18053-18057 ◽  
Author(s):  
Katherine M. Nautiyal ◽  
Ana C. Ribeiro ◽  
Donald W. Pfaff ◽  
Rae Silver
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Neural Systems ◽  
Loss Of Function ◽  
Littermate Control ◽  
Cytokines And Chemokines ◽  
Function Models ◽  
The Brain

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient KitW−sh/W−sh (sash−/−) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links.

Association of Mast Cell Burden and TIM-3 Expression with Recalcitrant Chronic Rhinosinusitis with Nasal Polyps

2021 ◽  
pp. 000348942199503
Author(s):  
Michael A. Belsky ◽  
Erica Corredera ◽  
Hridesh Banerjee ◽  
John Moore ◽  
Li Wang ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Cell Activation ◽  
Enzymatic Digestion ◽  
Sinus Surgery ◽  
Mast Cell Activation ◽  
Need For Treatment ◽  
Inflammatory State

Objectives: Previous work showed that higher polyp mast cell load correlated with worse postoperative endoscopic appearance in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyp epithelial mast cells showed increased expression of T-cell/transmembrane immunoglobulin and mucin domain protein 3 (TIM-3), a receptor that promotes mast cell activation and cytokine production. In this study, CRSwNP patients were followed post-operatively to investigate whether mast cell burden or TIM-3 expression among mast cells can predict recalcitrant disease. Methods: Nasal polyp specimens were obtained via functional endoscopic sinus surgery (FESS) and separated into epithelial and stromal layers via enzymatic digestion. Mast cells and TIM-3-expressing mast cells were identified via flow cytometry. Mann-Whitney U tests and Cox proportional hazard models assessed whether mast cell burden and TIM-3 expression were associated with clinical outcomes, including earlier recurrence of polypoid edema and need for treatment with steroids. Results: Twenty-three patients with CRSwNP were studied and followed for 6 months after undergoing FESS. Higher mast cell levels were associated with earlier recurrence of polypoid edema: epithelial HR = 1.283 ( P = .02), stromal HR = 1.103 ( P = .02). Percent of mast cells expressing TIM-3 in epithelial or stromal layers was not significantly associated with earlier recurrence of polypoid edema. Mast cell burden and TIM-3+ expression were not significantly associated with need for future treatment with steroids post-FESS. Conclusions: Mast cell load in polyp epithelium and stroma may predict a more refractory postoperative course for CRSwNP patients. The role of TIM-3 in the chronic inflammatory state seen in CRSwNP remains unclear.

Abstract 1193: Mast Cell Activation Promotes Leukocyte Recruitment And Adhesion To The Atherosclerotic Plaque

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Ilze Bot ◽  
Saskia C de Jager ◽  
Alma Zernecke ◽  
Christian Weber ◽  
Theo J van Berkel ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Cell Activation ◽  
Ex Vivo ◽  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Mast Cell Activation ◽  
Labeled Leukocytes

Activated mast cells have been identified in the perivascular tissue of human coronary artery plaques. As mast cells have been described to release a whole array of chemokines including interleukin 8 (IL-8) and MIP1 α, we propose that activated mast cells play a pivotal role in leukocyte recruitment at advanced stages of atherosclerotic plaque development. Peritoneal mast cells of either C57Bl/6 or mast cell deficient Kit(W −sh /W −sh ) mice were activated by injection of compound 48/80 (1.2 mg/kg). Interestingly, mast cell activation led to a massive neutrophil influx into the peritoneal cavity at 3 hours after activation (controls: 1 ± 0.7*10 4 Gr1 + -neutrophils/ml up to 8 ± 0.2*10 4 Gr1 + neutrophils/ml at 3 hours after activation, *P<0.05), while neutrophil numbers in Kit(W −sh /W −sh ) mice were not affected by compound 48/80 administration. Moreover, increased levels of CXCR2 + Gr1 + neutrophils (t=0: 0.55 ± 0.07% versus t=3 hours: 1.00 ± 0.12%, *P<0.05) were observed after mast cell activation. Next, we investigated whether mast cell activation also translated in induced leukocyte adhesion to advanced atherosclerotic plaques. Adventitial mast cells of advanced collar aided carotid artery plaques were activated by local application of a dinitrophenyl-BSA (DNP) challenge in ApoE −/− mice. Three days later, the carotid artery segments carrying the plaques were isolated and perfused ex vivo with rhodamine labeled leukocytes, showing a dramatically increased number of adherent leukocytes after mast cell activation (49 ± 6 versus 19 ± 4 leukocytes/microscopic field for DNP versus control plaques, respectively, **P<0.001). Strikingly, antibody blockade of either the CXCR2 or VCAM-1 receptor VLA-4 on labeled leukocytes completely inhibited leukocyte adhesion to the atherosclerotic plaque (*P<0.05), while blockade of CCR1, -3 and -5 with Met-RANTES had no effect. In conclusion, our data suggest that chemokines such as IL-8 released from activated perivascular mast cells induce leukocyte recruitment and adhesion to the atherosclerotic plaque, aggravating the ongoing inflammatory response and thus effecting plaque destabilization. We propose that mast cell stabilization could be a new therapeutic approach in the prevention of acute coronary syndromes.

scholarly journals Mast cell activation is not required for induction of airway hyperresponsiveness by ozone in mice

1999 ◽  
Vol 86 (1) ◽  
pp. 202-210 ◽  
Author(s):  
N. Noviski ◽  
J. P. Brewer ◽  
W. A. Skornik ◽  
S. J. Galli ◽  
J. M. Drazen ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Airway Hyperresponsiveness ◽  
Essential Role ◽  
Cell Activation ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Polymorphonuclear Cell ◽  
Pulmonary Parenchyma

Exposure to ambient ozone (O3) is associated with increased exacerbations of asthma. We sought to determine whether mast cell degranulation is induced by in vivo exposure to O3in mice and whether mast cells play an essential role in the development of pulmonary pathophysiological alterations induced by O3. For this we exposed mast cell-deficient WBB6F1- kitW/ kitW-v( kitW/ kitW-v) mice and the congenic normal WBB6F1(+/+) mice to air or to 1 or 3 parts/million O3for 4 h and studied them at different intervals from 4 to 72 h later. We found evidence of O3-induced cutaneous, as well as bronchial, mast cell degranulation. Polymorphonuclear cell influx into the pulmonary parenchyma was observed after exposure to 1 part/milllion O3only in mice that possessed mast cells. Airway hyperresponsiveness to intravenous methacholine measured in vivo under pentobarbital anesthesia was observed in both kitW/ kitW-vand +/+ mice after exposure to O3. Thus, although mast cells are activated in vivo by O3and participate in O3-induced polymorphonuclear cell infiltration into the pulmonary parenchyma, they do not participate detectably in the development of O3-induced airway hyperresponsiveness in mice.

scholarly journals Granzyme D Is a Novel Murine Mast Cell Protease That Is Highly Induced by Multiple Pathways of Mast Cell Activation

2013 ◽  
Vol 81 (6) ◽  
pp. 2085-2094 ◽  
Author(s):  
Elin Rönnberg ◽  
Gabriela Calounova ◽  
Bengt Guss ◽  
Anders Lundequist ◽  
Gunnar Pejler
Keyword(s):  
T Cells ◽  
Mast Cell ◽  
Mast Cells ◽  
Serine Proteases ◽  
Cell Activation ◽  
Calcium Ionophore ◽  
Mast Cell Activation ◽  
Activated T Cells ◽  
Mast Cell Protease ◽  
Murine Mast Cell

ABSTRACTGranzymes are serine proteases known mostly for their role in the induction of apoptosis. Granzymes A and B have been extensively studied, but relatively little is known about granzymes C to G and K to M. T cells, lymphohematopoietic stromal cells, and granulated metrial gland cells express granzyme D, but the function of granzyme D is unknown. Here we show that granzyme D is expressed by murine mast cells and that its level of expression correlates positively with the extent of mast cell maturation. Coculture of mast cells with live, Gram-positive bacteria caused a profound, Toll-like receptor 2 (TLR2)-dependent induction of granzyme D expression. Granzyme D expression was also induced by isolated bacterial cell wall components, including lipopolysaccharide (LPS) and peptidoglycan, and by stem cell factor, IgE receptor cross-linking, and calcium ionophore stimulation. Granzyme D was released into the medium in response to mast cell activation. Granzyme D induction was dependent on protein kinase C and nuclear factor of activated T cells (NFAT). Together, these findings identify granzyme D as a novel murine mast cell protease and implicate granzyme D in settings where mast cells are activated, such as bacterial infection and allergy.

Sign in / Sign up

Export Citation Format

Share Document