scholarly journals Tanshinone IIA improves degranulation of mast cells and allergic rhinitis induced by ovalbumin by inhibiting the PLCγ1/PKC/IP3R pathway

2021 ◽  
pp. 096032712110588
Author(s):  
Shouye Li ◽  
Zheming Li ◽  
Tao Tan ◽  
Shijie Dai ◽  
Yangsheng Wu ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Salvia Miltiorrhiza ◽  
Vital Role ◽  
Tanshinone Iia ◽  
Ar Model ◽  
Blue Staining ◽  
Phospholipase Cγ1 ◽  
Safranin O

Allergic rhinitis (AR) is a common allergic inflammatory and chronic reactive disease caused by allergen-induced immunoglobulin E (IgE). Tanshinone IIA (Tan IIA) is one of the active ingredients in Salvia miltiorrhiza Bunge (Danshen) and plays a vital role in inhibiting inflammation. Thus, we hypothesized that Tan IIA has anti-allergic effects and studied the function of Tan IIA in mast cells and an AR animal model. We induced RBL-2H3 cell sensitization with monoclonal anti-2,4,6-dinitrophenyl-immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA) and constructed an ovalbumin (OVA)-induced AR model in mice. The role of Tan IIA in AR progression was studied using the MTT assay, ELISA, western blot, toluidine blue staining, HE staining, and Alcian blue and safranin O (A&S) staining. Tan IIA treatment significantly increased IgE/HSA-induced cell viability. However, Tan IIA treatment markedly downregulated the expression levels of β-hexosaminidase, histamine, tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), IL-4, and IL-5 in IgE/HSA-induced cells. Furthermore, Tan IIA improved typical symptoms in the OVA-induced AR model mice by inhibiting the phospholipase Cγ1 (PLCγ1)/protein kinase C (PKC)/IP3R pathway. Additionally, Tan IIA effectively improved the degranulation of RBL-2H3 cells and OVA-induced AR in mice. Together, these results suggest that Tan IIA may be a potential drug for the treatment of AR in the future.

The Inferior Turbinate Mast Cell Population of Patients with Perennial Allergic and Nonallergic Rhinitis

1997 ◽  
Vol 11 (1) ◽  
pp. 63-66 ◽  
Author(s):  
Gilead Berger ◽  
Arnon Goldberg ◽  
Dov Ophir
Keyword(s):  
Allergic Rhinitis ◽  
Mast Cell ◽  
Mast Cells ◽  
Inferior Turbinate ◽  
Blue Staining ◽  
Perennial Allergic Rhinitis ◽  
Nonallergic Rhinitis ◽  
Cell Counts ◽  
Significant Difference ◽  
Normal Controls

The number of mast cells in the inferior turbinates of patients with perennial allergic rhinitis and perennial nonallergic rhinitis was compared with normal controls. Mast cell counts expressed as the mean number in 100 high-power fields, assessed after Carnoy's fixation and toluidine blue staining were 1.84 in normal controls (n = 11), 4.39 in patients with perennial allergic rhinitis (n = 13), and 4.00 in those with perennial nonallergic rhinitis (n = 26). Statistical analysis confirmed that the density of mast cells in allergic as well as in nonallergic patients was significantly higher than in normal controls, whereas no significant difference was found between the number of mast cells in allergic and nonallergic patients. It is concluded that the number of mast cells in the inferior turbinate mucosa of patients with perennial rhinitis is increased compared with normal controls, and the increased number is not necessarily allergy-dependent.

scholarly journals Aging-associated shifts in functional status of mast cells located by adult and aged mesenteric lymphatic vessels

2012 ◽  
Vol 303 (6) ◽  
pp. H693-H702 ◽  
Author(s):  
Victor Chatterjee ◽  
Anatoliy A. Gashev
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Functional Status ◽  
Toluidine Blue ◽  
Immunoglobulin E ◽  
Transmembrane Protein ◽  
Lymphatic Vessels ◽  
Mast Cell Activation ◽  
Blue Staining ◽  
Rat Mesentery

We had previously proposed the presence of permanent stimulatory influences in the tissue microenvironment surrounding the aged mesenteric lymphatic vessels (MLV), which influence aged lymphatic function. In this study, we performed immunohistochemical labeling of proteins known to be present in mast cells (mast cell tryptase, c-kit, prostaglandin D2 synthase, histidine decarboxylase, histamine, transmembrane protein 16A, and TNF-α) with double verification of mast cells in the same segment of rat mesentery containing MLV by labeling with Alexa Fluor 488-conjugated avidin followed by toluidine blue staining. Additionally, we evaluated the aging-associated changes in the number of mast cells located by MLV and in their functional status by inducing mast cell activation by various activators (substance P; anti-rat DNP Immunoglobulin E; peptidoglycan from Staphyloccus aureus and compound 48/80) in the presence of ruthenium red followed by subsequent staining by toluidine blue. We found that there was a 27% aging-associated increase in the total number of mast cells, with an ∼400% increase in the number of activated mast cells in aged mesenteric tissue in resting conditions with diminished ability of mast cells to be newly activated in the presence of inflammatory or chemical stimuli. We conclude that higher degree of preactivation of mast cells in aged mesenteric tissue is important for development of aging-associated impairment of function of mesenteric lymphatic vessels. The limited number of intact aged mast cells located close to the mesenteric lymphatic compartments to react to the presence of acute stimuli may be considered contributory to the aging-associated deteriorations in immune response.

scholarly journals MicroRNA-29 mediates anti-inflammatory effects and alleviation of allergic responses and symptoms in mice with allergic rhinitis

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Jia Wang ◽  
Jinshu Yin ◽  
Hong Peng ◽  
Aizhu Liu
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Immunoglobulin E ◽  
Underlying Mechanism ◽  
Lavage Fluid ◽  
Specific Ige ◽  
Ar Model ◽  
Protein Levels ◽  
Mucosa Cell

Abstract Background To investigate the role of microRNA-29 (miR-29) in mice with allergic rhinitis (AR) and its underlying mechanism. Methods AR model was established in BALB/c mice by intraperitoneal sensitization and intranasal challenge with ovalbumin (OVA). miRNA expression was examined in the nasal mucosa tissues of mice and patients with AR, and miRNA-29 was found to be downregulated. To unveil the role of miRNA-29 in AR, it was overexpressed in the nasal mucosa of AR mice by intranasal administration of miRNA-29 agomir. The symptoms of nasal rubbing and sneezing were recorded and evaluated. miR-29 expression, OVA-specific immunoglobulin E (IgE) concentration, pro-inflammatory cytokines levels, eosinophils number, and cleaved caspase-3 and CD276 expression were examined in nasal mucosa tissues and nasal lavage fluid (NALF) by qRT-PCR, ELISA, hematoxylin and eosin staining, western blotting, or immunohistochemistry, respectively. TUNEL assay was used to analyze nasal mucosa cells apoptosis. Results Decreased expression of miR-29 was observed in AR, the symptoms of which were alleviated by overexpressing miR-29. In addition, overexpression of miR-29 markedly reduced the concentration of OVA-specific IgE, the levels of IL-4, IL-6, IL-10, and IFN-γ, the pathological alterations and eosinophils infiltration in the nasal mucosa. Furthermore, restoration of miR-29 expression reduced nasal mucosa cell apoptosis. Moreover, overexpression of miR-29 significantly attenuated CD276 mRNA and protein levels in nasal mucosa cells. Conclusion MiR-29 mediated antiallergic effects in OVA-induced AR mice by decreasing inflammatory response, probably through targeting CD276. MiRNA-29 may serve as a potential novel therapeutic target for the treatment of AR.

scholarly journals MicroRNA-133b Ameliorates Allergic Inflammation and Symptom in Murine Model of Allergic Rhinitis by Targeting Nlrp3

2017 ◽  
Vol 42 (3) ◽  
pp. 901-912 ◽  
Author(s):  
Lifeng Xiao ◽  
Li Jiang ◽  
Qi Hu ◽  
Yuru Li
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Mucosa ◽  
Nlrp3 Inflammasome ◽  
Immunoglobulin E ◽  
Ar Model ◽  
Allergic Symptom ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Tnf Α ◽  
Ifn Γ

Background: Emerging evidences indicate that post-transcriptional regulation by microRNAs is critical in allergic rhinitis (AR) pathogenesis. MircroRNA-133b (miR-133b) was recently suggested as a potential predictor of AR. However, the in vivo effect of miR-133b on AR is unclear. Methods: AR model was established in BALB/c mice by intraperitoneal sensitization and intranasal challenge with ovalbumin (OVA). MiR-133b agomir was then intranasally administrated to mice after OVA challenge for another 7 days. The symptom of nasal rubbing and sneezing were recorded after the last OVA challenge. Nasal mucosa tissues and serum were collected. MiR-133b expression, serum OVA-specific immunoglobulin E (IgE) concentration, proinflammatory cytokines (TNF-α, IL-4, IL-5, IL-10 and IFN-γ) levels, and Nlrp3 inflammasome activation were measured by RT-PCR, ELISA, western blotting or immunohistochemistry, respectively. Histopathologic changes were evaluated using hematoxylin and eosin and Sirius red staining. The luciferase activity and protein expression of Nlrp3 were also determined. Results: MiR-133b expression was significantly decreased in nasal mucosa of AR mice, which was restored by nasal administration with miR-133b agomir. Upregulation of miR-133b markedly reduced the concentration of OVA-specific IgE, the frequencies of nasal rubbing and sneezing, and the levels of cytokines (TNF-α, IL-4, IL-5 and IFN-γ). Levels of IL-4, IL-5, IL-10 and IFN-γ produced by cervical lymph node cells were significantly lowered in miR-133b agomir-treated mice. Moreover, miR-133b also appeared to strongly attenuate pathological alterations and eosinophils and mast cells infiltration in nasal mucosa. Notably, we demonstrated for the first time that miR-133b negatively regulated Nlrp3 expression through binding with the 3’ untranslated region of Nlrp3. Consequently, infection of miR-133b in nasal mucosa remarkably suppressed the Nlrp3 inflammasome activation, as evidenced by reduced Nlrp3, Caspase-1, ASC, IL-18 and IL-1 expressions. Conclusion: MiR-133b alleviates allergic symptom in AR mice by inhibition of Nlrp3 inflammasome-meditated inflammation. These findings provide us an insight into the potential role of miR-133b in relation to AR treatment.

Serum immunoglobulin E reactivity to cross-reacting panallergen components in north-eastern Poland patients pollen sensitized

2020 ◽  
Vol 41 (3) ◽  
pp. 183-191
Author(s):  
Krzysztof Kowal ◽  
Agnieszka Pampuch ◽  
Ewa Sacharzewska ◽  
Ewa Swiebocka ◽  
Zenon Siergiejko ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Allergen Immunotherapy ◽  
Immunoglobulin E ◽  
Pollen Allergy ◽  
Serum Ige ◽  
Ige Reactivity ◽  
Allergen Components ◽  
North Eastern ◽  
Allergen Sources ◽  
Seasonal Pollen

Background: The presence of immunoglobulin E (IgE), which cross-reacts with allergen components, such as profilins, polcalcins, and cross-reacting carbohydrate determinants (CCD), creates a problem when selecting patients for allergen immunotherapy by using conventional methods. The aim of this study was to evaluate the prevalence of sensitization to profilins, polcalcins, and CCDs in patients with seasonal pollen allergic rhinitis. Methods: The study was performed on a group of 112 patients with seasonal pollen allergic rhinitis, ages 14 to 55 years, with sensitization to at least one seasonal allergen (IgE > 0.7 kUA/L). The presence of IgE sensitization to recombinant (r) Bet v 2, rPhl p 12, rBet v 4, rPhl p 7, and CCDs, in addition to rBet v 1, rPhl p 1, rPhl p 5, was evaluated by using a multiparameter immunoblot. Results: Among the studied patients, 64.3, 80.4, and 41.1% were sensitized to birch, timothy grass, and mugwort pollen, respectively. Sensitization to profilins rBet v 2/Phl p 12 was demonstrated in 28.6%, to polcalcins Bet v 4/Phl p 7 in 8.9%, and to CCDs in 25%. In 29.3%, serum IgE reactivity to any of the cross-reactive components could be demonstrated. Serum IgE reactivity to rBet v 2 was always accompanied by IgE reactivity to rPhl p 12, and IgE reactivity to rBet v 4 was always accompanied by IgE reactivity to rPhl p 7. Among the patients with pollinosis co-sensitized to at least two allergen sources according to extract-based diagnosis, possible false-positive results due to sensitization to cross-reactive components were detected in 17.9%. Conclusion: Evaluation of sensitization to cross-reacting components may be useful in evaluation of patients with pollen allergy who are being assessed for allergen immunotherapy to optimize the constitution of their immunotherapy vaccines.

scholarly journals Ubiquitous Overexpression of Chromatin Remodeling Factor SRG3 Exacerbates Atopic Dermatitis in NC/Nga Mice by Enhancing Th2 Immune Responses

2021 ◽  
Vol 22 (4) ◽  
pp. 1553
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Jungmin Jeon ◽  
Yun Hoo Park ◽  
Tae-Cheol Kim ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cells ◽  
Immune Responses ◽  
Chromatin Remodeling ◽  
Skin Diseases ◽  
Immunoglobulin E ◽  
Critical Role ◽  
Interleukin 4 ◽  
Inflammatory Skin Diseases ◽  
Immune Disorder

The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder. Thus, to elucidate the effects of SRG3 overexpression in AD development, we bred NC/Nga (NC) mice with transgenic mice where SRG3 expression is driven by the β-actin promoter (SRG3β-actin mice). We found that SRG3β-actin NC mice exhibit increased AD development (e.g., a higher clinical score, immunoglobulin E (IgE) hyperproduction, and an increased number of infiltrated mast cells and basophils in skin lesions) compared with wild-type NC mice. Moreover, the severity of AD pathogenesis in SRG3β-actin NC mice correlated with expansion of interleukin 4 (IL4)-producing basophils and mast cells, and M2 macrophages. Furthermore, this accelerated AD development is strongly associated with Treg cell suppression. Collectively, our results have identified that modulation of SRG3 function can be applied as one of the options to control AD pathogenesis.

scholarly journals Tanshinones induce tumor cell apoptosis via directly targeting FHIT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xianglian Zhou ◽  
Yuting Pan ◽  
Yue Wang ◽  
Bojun Wang ◽  
Yu Yan ◽  
...  
Keyword(s):  
Salvia Miltiorrhiza ◽  
Water Soluble ◽  
Tanshinone Iia ◽  
Binding Affinities ◽  
Tumor Cell Apoptosis ◽  
Anti Cancer ◽  
Sodium Tanshinone Iia Sulfonate ◽  
Direct Binding ◽  
Fhit Protein ◽  
Diadenosine Triphosphate

AbstractThe liposoluble tanshinones are bioactive components in Salvia miltiorrhiza and are widely investigated as anti-cancer agents, while the molecular mechanism is to be clarified. In the present study, we identified that the human fragile histidine triad (FHIT) protein is a direct binding protein of sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of Tanshinone IIA (TSA), with a Kd value of 268.4 ± 42.59 nM. We also found that STS inhibited the diadenosine triphosphate (Ap3A) hydrolase activity of FHIT through competing for the substrate-binding site with an IC50 value of 2.2 ± 0.05 µM. Notably, near 100 times lower binding affinities were determined between STS and other HIT proteins, including GALT, DCPS, and phosphodiesterase ENPP1, while no direct binding was detected with HINT1. Moreover, TSA, Tanshinone I (TanI), and Cryptotanshinone (CST) exhibited similar inhibitory activity as STS. Finally, we demonstrated that depletion of FHIT significantly blocked TSA’s pro-apoptotic function in colorectal cancer HCT116 cells. Taken together, our study sheds new light on the molecular basis of the anti-cancer effects of the tanshinone compounds.

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