Mast cells release cytokines in response to mediators produced by virus-infected epithelial cellss

2007 ◽  
Vol 30 (4) ◽  
pp. 96
Author(s):  
Candy Tsang ◽  
A. D. Befus
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Epithelial Cells ◽  
Viral Infections ◽  
Allergic Diseases ◽  
Type I Interferons ◽  
Human Mast Cell ◽  
Type I ◽  
Dependent Manner ◽  
Tlr Agonists

Background: Mast cells have long been recognized for their involvement in allergic diseases. In the last decade, the importance of mast cells in innate responses against bacteria has been established, but little is known about their contribution in viral infections. Mast cells are abundant at mucosal surfaces such as the lungs in close proximity to the epithelium. In the lung, the epithelium is a primary target for viral infections. Mast cells are secondarily exposed to newly formed virions released from epithelial cells. Mast cells have toll-like receptors (TLRs) that detect various pathogen components. Our first hypothesis is that viral TLR agonists will induce mast cells to release cytokines thought to be involved in viral infections. Both the pro-inflammatory cytokine IL-6 and the chemokine IL-8 are produced during viral infections. TGF-β is an immunoregulatory cytokine that modulates the activity of various immune cells and could also play a role in viral infections. Methods: We used polyI:C, a synthetic double-stranded RNA (dsRNA), as a TLR3 agonist, loxoribine as a TLR7 agonist, and unmethylated CpG DNA as a TLR9 agonist. We treated mast cells from the cell line HMC-1 (Human Mast cell-1) for 0.5 – 24hr with the TLR agonists and performed dose response studies for all stimuli. Supernatants from treated mast cells were measured for IL-6, IL-8, and TGF-β by ELISA. Results: Cytokine release was highest at the 24hr time point. Mast cells released IL-6, IL-8, and TGF-β in response to the TLR3 agonist polyI:C in a dose-dependent manner, but not to the other viral TLR agonists. PolyI:C (10μg/mL) versus unstimulated controls significantly increased mast cell release of IL-6 (224.7±57.4 vs. 39.0±5.7, p≤0.001) and TGF-β (240.2±28.9 vs. 116.1±16.7, p≤0.05). PolyI:C induced release of IL-8 from mast cells was increased but not significant. Viral exposure also induces epithelial cells to produce type I interferons, IFNα and β. These interferons have potent antiviral activity, but also have effects on mast cells, decreasing mast cell adhesion to extracellular matrix and reducing co-stimulatory activity on T cells. Our second hypothesis is that IFNα and β will induce mast cells to release cytokines similar to stimulation with polyI:C. Our preliminary data showed that IFNα, IFNβ , and IFNα and β in combination induced a low level of IL-8 and TGF-β release from mast cells, but had no effect on IL-6 release. Conclusion: HMC-1 responds to dsRNA, a TLR3 agonist produced in epithelial cells during viral replication, by releasing IL-6 and TGF-β. HMC-1 also responds to IFNα and β by releasing IL-8 and TGF-β, indicating that human mast cells respond to epithelial mediators produced during viral infections. Our results show that mast cells contribute to the innate response against viruses by responding to mediators released by virus-infected epithelial cells.

scholarly journals Oral Administration of Fucoidan Can Exert Anti-Allergic Activity after Allergen Sensitization by Enhancement of Galectin-9 Secretion in Blood

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 258 ◽  
Author(s):  
Masashi Mizuno ◽  
Kana Sakaguchi ◽  
Iwao Sakane
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Epithelial Cells ◽  
Oral Administration ◽  
Therapeutic Agent ◽  
Allergic Diseases ◽  
Mast Cell Degranulation ◽  
Type I ◽  
Colonic Epithelial Cells ◽  
Mast Cell Line

A previous study revealed that fucoidan inhibited mast cell degranulation through the upregulation of galectin-9 in blood. The purpose of this study is to elucidate its mechanism using ovalbumin (OVA) induced anaphylaxis model mice (BALB/c, Female, 5-week-old) and mast cell line (RBL-2H3 cells). Oral administration of fucoidan after sensitization with OVA/Al(OH)3 inhibited reduction of rectal temperature induced by activation of mast cells. Fucoidan increased galectin-9 mRNA expression only in colonic epithelial cells. These results suggested that fucoidan could suppress the allergic symptoms in sensitized mice by inducing galectin-9 production from colonic epithelial cells. In addition, to check the influence of galectin 9 on the degranulation of mast cells, RBL-2H3 cell lines were treated directly with recombinant galectin-9. As expected, galectin-9 inhibited degranulation of RBL-2H3 cells pre-bound with IgE. Moreover, the residual amounts of IgE on RBL-2H3 cells were decreased by an addition of galectin-9. It was demonstrated that galectin-9 could remove IgE even if IgE was already bound to mast cells and suppress the mast cells degranulation induced by antigen. This study shows that fucoidan might become an effective therapeutic agent for patients already developed type I allergic diseases.

scholarly journals Alisol B 23-Acetate Inhibits IgE/Ag-Mediated Mast Cell Activation and Allergic Reaction

2018 ◽  
Vol 19 (12) ◽  
pp. 4092 ◽  
Author(s):  
Chen Shao ◽  
Bingjie Fu ◽  
Ning Ji ◽  
Shunli Pan ◽  
Xiaoxia Zhao ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Allergic Reaction ◽  
Nuclear Factor Kappa B ◽  
Immunoglobulin E ◽  
Mast Cell Activation ◽  
Human Mast Cell ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa

Alisol B 23-acetate (AB23A), a natural triterpenoid, has been reported to exert hepatoprotective and antitumor activities. Aiming to investigate the anti-inflammatory activity, this study examined the effect of AB23A on mast cells and allergic reaction. AB23A inhibited the degranulation of mast cells stimulated by immunoglobulin E/antigen (IgE/Ag), and also decreased the synthesis of leukotriene C4 (LTC4), production of interlukin-6 (IL-6), and expression of cyclooxygenase-2 (COX-2) in a concentration-dependent manner with no significant cytotoxicity in bone marrow-derived mast cells (BMMCs). AB23A inhibited spleen tyrosine kinase (Syk) and the downstream signaling molecules including phospholipase Cγ (PLCγ), serine-threonine protein kinase/inhibitor of nuclear factor kappa-B kinase/nuclear factor kappa-B (Akt/IKK/NF-κB), and mitogen-activated protein kinases/cytosolic phospholipase A2 (MAPK/cPLA2). Furthermore, AB23A blocked mobilization of Ca2+. Similar results were obtained in other mast cell lines Rat basophilic leukemia (RBL)-2H3 cells and a human mast cell line (HMC-1). In addition, AB23A attenuated allergic responses in an acute allergy animal model, passive cutaneous anaphylaxis (PCA). Taken together, this study suggests that AB23A inhibits the activation of mast cells and ameliorates allergic reaction, and may become a lead compound for the treatment of mast cell-mediated allergic diseases.

scholarly journals The activation of bystander CD8+ T cells and their roles in viral infection

2019 ◽  
Vol 51 (12) ◽  
pp. 1-9 ◽  
Author(s):  
Tae-Shin Kim ◽  
Eui-Cheol Shin
Keyword(s):  
T Cells ◽  
Viral Infections ◽  
Hepatitis A Virus ◽  
Tissue Injury ◽  
Strong Association ◽  
Killer Cell ◽  
Type I Interferons ◽  
Type I ◽  
Dependent Manner ◽  
Bystander Activation

AbstractDuring viral infections, significant numbers of T cells are activated in a T cell receptor-independent and cytokine-dependent manner, a phenomenon referred to as “bystander activation.” Cytokines, including type I interferons, interleukin-18, and interleukin-15, are the most important factors that induce bystander activation of T cells, each of which plays a somewhat different role. Bystander T cells lack specificity for the pathogen, but can nevertheless impact the course of the immune response to the infection. For example, bystander-activated CD8+ T cells can participate in protective immunity by secreting cytokines, such as interferon-γ. They also mediate host injury by exerting cytotoxicity that is facilitated by natural killer cell-activating receptors, such as NKG2D, and cytolytic molecules, such as granzyme B. Interestingly, it has been recently reported that there is a strong association between the cytolytic function of bystander-activated CD8+ T cells and host tissue injury in patients with acute hepatitis A virus infection. The current review addresses the induction of bystander CD8+ T cells, their effector functions, and their potential roles in immunity to infection, immunopathology, and autoimmunity.

scholarly journals Mast Cell Responses to Viruses and Pathogen Products

2019 ◽  
Vol 20 (17) ◽  
pp. 4241 ◽  
Author(s):  
Jean S. Marshall ◽  
Liliana Portales-Cervantes ◽  
Edwin Leong
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immune Responses ◽  
Viral Infection ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Local Source ◽  
Type I ◽  
Viral Challenge ◽  
Cell Responses

Mast cells are well accepted as important sentinel cells for host defence against selected pathogens. Their location at mucosal surfaces and ability to mobilize multiple aspects of early immune responses makes them critical contributors to effective immunity in several experimental settings. However, the interactions of mast cells with viruses and pathogen products are complex and can have both detrimental and positive impacts. There is substantial evidence for mast cell mobilization and activation of effector cells and mobilization of dendritic cells following viral challenge. These cells are a major and under-appreciated local source of type I and III interferons following viral challenge. However, mast cells have also been implicated in inappropriate inflammatory responses, long term fibrosis, and vascular leakage associated with viral infections. Progress in combating infection and boosting effective immunity requires a better understanding of mast cell responses to viral infection and the pathogen products and receptors we can employ to modify such responses. In this review, we outline some of the key known responses of mast cells to viral infection and their major responses to pathogen products. We have placed an emphasis on data obtained from human mast cells and aim to provide a framework for considering the complex interactions between mast cells and pathogens with a view to exploiting this knowledge therapeutically. Long-lived resident mast cells and their responses to viruses and pathogen products provide excellent opportunities to modify local immune responses that remain to be fully exploited in cancer immunotherapy, vaccination, and treatment of infectious diseases.

Retinoic acid is a negative regulator for the differentiation of cord blood-derived human mast cell progenitors

Blood ◽  
2000 ◽  
Vol 95 (9) ◽  
pp. 2821-2828 ◽  
Author(s):  
Tatsuya Kinoshita ◽  
Kenichi Koike ◽  
Hadija Hemed Mwamtemi ◽  
Susumu Ito ◽  
Shuichi Ishida ◽  
...  
Keyword(s):  
Mast Cell ◽  
Retinoic Acid ◽  
Mast Cells ◽  
Cord Blood ◽  
Cell Development ◽  
Negative Regulator ◽  
Human Mast Cell ◽  
Target Cells ◽  
Dependent Manner ◽  
Selective Agonist

We examined the effects of retinoids on the human mast cell development using a serum-deprived culture system. When 10-week cultured mast cells derived from CD34+ cord blood cells were used as target cells, both all-trans retinoic acid (ATRA) and 9-cis RA inhibited the progeny generation under stimulation with stem cell factor (SCF) in a dose-dependent manner (the number of progeny grown by SCF plus RA at 10−7 mol/L was one tenth of the value obtained by SCF alone). The early steps in mast cell development appear to be less sensitive to RA according to the single CD34+c-kit+ cord blood cell culture study. The optimal concentration of RAs also reduced the histamine concentration in the cultured mast cells (3.00 ± 0.47 pg per cell in SCF alone, 1.44 ± 0.18 pg per cell in SCF+ATRA, and 1.41 ± 0.10 pg per cell in SCF+9-cis RA). RT-PCR analyses showed the expression of RAR, RARβ, RXR, and RXRβ messenger ribonucleic acid (mRNA) in 10-week cultured mast cells. The addition of an RAR-selective agonist at 10−10 mol/L to 10−7 mol/L decreased the number of mast cells grown in SCF, whereas an RXR-selective agonist at up to 10−8 mol/L was inactive. Among RAR subtype selective retinoids used at 10−9 mol/L to 10−7 mol/L, only the RAR agonist was equivalent to ATRA at 10−7 mol/L in its ability to inhibit mast cell growth. Conversely, the addition of excess concentrations of a RAR antagonist profoundly counteracted the retinoid-mediated suppressive effects. These results suggest that RA inhibits SCF-dependent differentiation of human mast cell progenitors through a specific receptor.

scholarly journals Hypoxia modulates human mast cell adhesion to hyaluronic acid

2021 ◽  
Author(s):  
Joanna Pastwińska ◽  
Aurelia Walczak-Drzewiecka ◽  
Elżbieta Kozłowska ◽  
Enjuro Harunari ◽  
Marcin Ratajewski ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mast Cell ◽  
Hyaluronic Acid ◽  
Cell Adhesion ◽  
Mast Cells ◽  
Immune Cell ◽  
Human Mast Cell ◽  
Dependent Manner ◽  
Cell Functions ◽  
Extracellular Matrix Components

AbstractHypoxia is an inherent factor in the inflammatory process and is important in the regulation of some immune cell functions, including the expression of mast cell pro- and anti-inflammatory mediators. Hypoxia also influences cell adhesion to the extracellular matrix (ECM). Hyaluronic acid is one of the major components of the ECM that is involved in inflammatory and tissue regeneration processes in which mast cells play a prominent role. This prompted us to investigate the effects of hypoxia on the expression of hyaluronic acid receptors in mast cells and mast cell adhesion to this ECM component. We found that human LAD2 mast cells spontaneously adhered to hyaluronic acid in a CD44-dependent manner and that reduced oxygen concentrations inhibited or even completely abolished this adhesion process. The mechanism of hypoxia downregulation of mast cell adhesion to hyaluronic acid did not involve a decrease in CD44 expression and hyaluronidase-mediated degradation of adhesion substrates but rather conformational changes in the avidity of CD44 to hyaluronic acid. Hypoxia-mediated regulation of mast cell adhesion to extracellular matrix components might be involved in the pathogenic accumulation of mast cells observed in the course of certain diseases including rheumatoid arthritis and cancer.

scholarly journals Bacterial and Fungal Toll-Like Receptor Activation Elicits Type I IFN Responses in Mast Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Lisa Kornstädt ◽  
Sandra Pierre ◽  
Andreas Weigert ◽  
Stefanie Ebersberger ◽  
Tim J. Schäufele ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Allergic Diseases ◽  
Receptor Activation ◽  
Type I ◽  
Toll Like Receptor ◽  
Resolution Of Inflammation ◽  
Type I Ifns ◽  
Ige Mediated

Next to their role in IgE-mediated allergic diseases and in promoting inflammation, mast cells also have antiinflammatory functions. They release pro- as well as antiinflammatory mediators, depending on the biological setting. Here we aimed to better understand the role of mast cells during the resolution phase of a local inflammation induced with the Toll-like receptor (TLR)-2 agonist zymosan. Multiple sequential immunohistology combined with a statistical neighborhood analysis showed that mast cells are located in a predominantly antiinflammatory microenvironment during resolution of inflammation and that mast cell-deficiency causes decreased efferocytosis in the resolution phase. Accordingly, FACS analysis showed decreased phagocytosis of zymosan and neutrophils by macrophages in mast cell-deficient mice. mRNA sequencing using zymosan-induced bone marrow-derived mast cells (BMMC) revealed a strong type I interferon (IFN) response, which is known to enhance phagocytosis by macrophages. Both, zymosan and lipopolysaccharides (LPS) induced IFN-β synthesis in BMMCs in similar amounts as in bone marrow derived macrophages. IFN-β was expressed by mast cells in paws from naïve mice and during zymosan-induced inflammation. As described for macrophages the release of type I IFNs from mast cells depended on TLR internalization and endosome acidification. In conclusion, mast cells are able to produce several mediators including IFN-β, which are alone or in combination with each other able to regulate the phagocytotic activity of macrophages during resolution of inflammation.

scholarly journals DEF Cell-Derived Exosomal miR-148a-5p Promotes DTMUV Replication by Negative Regulating TLR3 Expression

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 94 ◽  
Author(s):  
Hongyan Guo ◽  
Anchun Cheng ◽  
Xingcui Zhang ◽  
YuHong Pan ◽  
Mingshu Wang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Viral Infections ◽  
Membrane Vesicles ◽  
Type I Interferons ◽  
Inflammatory Factors ◽  
Economic Losses ◽  
Type I ◽  
Dependent Manner ◽  
Replication Process ◽  
Type I Ifns

Duck tembusu virus (DTMUV) is a single-stranded, positive-polarity RNA flavivirus that has caused considerable economic losses in China in recent years. Innate immunity represents the first line of defense against invading pathogens and serves as an important role in resisting viral infections. In this study, we found that the infection of ducks by DTMUV triggers Toll-like receptors (TLRs) and (RIG-I)-like receptors (RLRs) signaling pathways and inducing abundant of pro-inflammatory factors and type I interferons (IFNs), in which melanoma differentiation-associated gene 5 (MDA5) and Toll-like receptor 3 (TLR3) play important immunity roles, they can inhibit the replication process of DTMUV via inducing type I IFNs. Moreover, we demonstrated that type I IFNs can inhibit the DTMUV replication process in a time- and dose-dependent manner. Exosomes are small membrane vesicles that have important roles in intercellular communication. MicroRNAs (miRNAs) are small non-coding RNAs that can modulate gene expression and are common substances in exosomes. In our experiment, we successfully isolated DEF cells derived exosome for the first time and explored its function. Firstly, we found the expression of miR-148a-5p is significantly decreased following DTMUV infect. Then we found miR-148a-5p can target TLR3 and down-regulate the expression of TLR3, serving as a negative factor in innate immunity. Unfortunately, we cannot find miRNAs with different expression changes that can target MDA5. Lastly, our experimental results showed that TLR3 was one of the causes of miR-148a-5p reduction, suggesting that the high level of TLR3 after DTMUV infect can both trigger innate immunity and suppress miR-148a-5p to resist DTMUV.

scholarly journals Interleukin-33 Amplifies Human Mast Cell Activities Induced by Complement Anaphylatoxins

2021 ◽  
Vol 11 ◽  
Author(s):  
Peter W. West ◽  
Rajia Bahri ◽  
Karen M. Garcia-Rodriguez ◽  
Georgia Sweetland ◽  
Georgia Wileman ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Allergic Diseases ◽  
Receptor Expression ◽  
Calcium Flux ◽  
Human Mast Cell ◽  
C5a Receptor ◽  
Interleukin 33 ◽  
Cell Responses ◽  
Human Mast Cells

Both, aberrant mast cell responses and complement activation contribute to allergic diseases. Since mast cells are highly responsive to C3a and C5a, while Interleukin-33 (IL-33) is a potent mast cell activator, we hypothesized that IL-33 critically regulates mast cell responses to complement anaphylatoxins. We sought to understand whether C3a and C5a differentially activate primary human mast cells, and probe whether IL-33 regulates C3a/C5a-induced mast cell activities. Primary human mast cells were generated from peripheral blood precursors or isolated from healthy human lung tissue, and mast cell complement receptor expression, degranulation, mediator release, phosphorylation patterns, and calcium flux were assessed. Human mast cells of distinct origin express constitutively higher levels of C3aR1 than C5aR1, and both receptors are downregulated by anaphylatoxins. While C3a is a potent mast cell degranulation inducer, C5a is a weaker secretagogue with more delayed effects. Importantly, IL-33 potently enhances the human mast cell reactivity to C3a and C5a (degranulation, cytokine and chemokine release), independent of changes in C3a or C5a receptor expression or the level of Ca2+ influx. Instead, this reflects differential dynamics of intracellular signaling such as ERK1/2 phosphorylation. Since primary human mast cells respond differentially to anaphylatoxin stimulation, and that IL-33 is a key regulator of mast cell responses to complement anaphylatoxins, this is likely to aggravate Th2 immune responses. This newly identified cross-regulation may be important for controlling exacerbated complement- and mast cell-dependent Th2 responses and thus provides an additional rationale for targeting anti-IL33 therapeutically in allergic diseases.

MMP dependence of fibroblast contraction and collagen production induced by human mast cell activation in a three-dimensional collagen lattice

2009 ◽  
Vol 296 (2) ◽  
pp. L236-L247 ◽  
Author(s):  
Alexander Margulis ◽  
Karl H. Nocka ◽  
Nancy L. Wood ◽  
Stanley F. Wolf ◽  
Samuel J. Goldman ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Three Dimensional ◽  
Mast Cell Activation ◽  
Human Mast Cell ◽  
Dependent Manner ◽  
Proteolytic Activation ◽  
Collagen Production ◽  
Collagen Lattice

Mast cell-fibroblast interactions may contribute to fibrosis in asthma and other disease states. Fibroblast contraction is known to be stimulated by coculture with the human mast cell line, HMC-1, or by mast cell-derived agents. Matrix metalloproteinases (MMPs) can also mediate contraction, but the MMP-dependence of mast cell-induced fibroblast contractility is not established, and the consequences of mast cell activation within the coculture system have not been fully explored. We demonstrate that activation of primary human mast cells (pHMC) with IgE receptor cross-linking, or activation of HMC-1 with C5a, enhanced contractility of human lung fibroblasts in a three-dimensional collagen lattice system. This enhanced contractility was inhibited by the pan-MMP antagonist, batimastat, and was transferrable in the conditioned medium of activated mast cells. Exogenously added MMPs promoted gel contraction by mediating the proteolytic activation of latent transforming growth factor-β (TGF-β). Consistent with this, fibroblast contraction induced by mast cell activation was enhanced by addition of excess latent TGF-β to the cultures. Batimastat inhibited this response, suggesting that MMPs capable of activating latent TGF-β were released following mast cell activation in coculture with fibroblasts. Collagen production was also stimulated by activated mast cells in an MMP-dependent manner. MMP-2 and MMP-3 content of the gels increased in the presence of activated mast cells, and inhibition of these enzymes blocked the contractile response. These findings demonstrate the MMP dependence of mast cell-induced fibroblast contraction and collagen production.

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