Displaying publications 1 - 20 of 23 in total

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  1. Chieng CCY, Daud HM, Yusoff FM, Thompson KD, Abdullah M
    J Fish Dis, 2020 Oct;43(10):1249-1258.
    PMID: 32830331 DOI: 10.1111/jfd.13222
    Groupers are popular aquaculture species in South-East Asia, but their cultivation is affected by infectious disease outbreaks. Mucosa-associated lymphoid tissues provide a first-line defence against pathogens; however, few studies are available relating to cellular or proteomic responses of mucosal immunity in grouper. Skin, gill and intestine were sampled from brown-marbled grouper Epinephelus fuscoguttatus (Forsskål, 1775) at 4 and 96 hr post-infection (hpi) and 7 days post-infection (dpi) following intraperitoneal infection with Vibrio harveyi, and stained with haematoxylin/eosin and Alcian Blue/periodic acid-Schiff. Skin mucus was analysed by 2D-gel electrophoresis, and proteins modulated by the bacterial infection identified. In the infected fish, significant increases in sacciform cells in skin and increased levels of nucleoside diphosphate kinase in mucus were detected at 4 hpi. At 96 hpi, goblet cells containing acidic mucins significantly increased in the intestine, while those containing mixed mucins increased in skin and gills of infected fish. Proteasome subunit alpha type-I and extracellular Cu/Zn superoxide dismutase levels also increased in mucus. Rodlet and mast cells did not appear to respond to the infection. Mucosal tissues of grouper appeared actively involved in response to Vibrio infection. This information may help future research on improving grouper health, production and vaccine development.
    Matched MeSH terms: Mast Cells
  2. Subramani T, Rathnavelu V, Yeap SK, Alitheen NB
    Mediators Inflamm, 2013;2013:275172.
    PMID: 23431239 DOI: 10.1155/2013/275172
    Mast cells (MCs) are multifunctional effector cells that were originally thought to be involved in allergic disorders. Now it is known that they contain an array of mediators with a multitude of effects on many other cells. MCs have become a recent concern in drug-induced gingival overgrowth (DIGO), an unwanted outcome of systemic medication. Most of the studies have confirmed the significant presence of inflammation as a prerequisite for the overgrowth to occur. The inflammatory changes within the gingival tissue appear to influence the interaction between the inducing drug and the fibroblast activity. The development of antibodies to MC-specific enzymes, tryptase and chymase, has facilitated the study of mast cells in DIGO. Many immunohistochemical studies involving MCs have been conducted; as a result, DIGO tissues are found to have increased the number of MCs in the gingiva, especially in the area of fibrosis. At the cellular level, gingival fibrogenesis is initiated by several mediators which induce the recruitment of a large number of inflammatory cells, including MCs. The purpose of this paper is to access the roles played by MCs in gingival overgrowth to hypothesize a relationship between these highly specialized cells in the pathogenesis of DIGO.
    Matched MeSH terms: Mast Cells/metabolism; Mast Cells/physiology*
  3. Sarchio SNE, Scolyer RA, Beaugie C, McDonald D, Marsh-Wakefield F, Halliday GM, et al.
    J Invest Dermatol, 2014 Apr;134(4):1091-1100.
    PMID: 24226205 DOI: 10.1038/jid.2013.424
    One way sunlight causes skin cancer is by suppressing anti-tumor immunity. A major mechanism involves altering mast cell migration via the C-X-C motif chemokine receptor 4-C-X-C motif chemokine ligand 12 (CXCR4-CXCL12) chemokine pathway. We have discovered that pharmacologically blocking this pathway with the CXCR4 antagonist AMD3100 prevents both UV radiation-induced immune suppression and skin cancer. The majority of control mice receiving UV-only developed histopathologically confirmed squamous cell carcinomas. In contrast, skin tumor incidence and burden was significantly lower in AMD3100-treated mice. Perhaps most striking was that AMD3100 completely prevented the outgrowth of latent tumors that occurred once UV irradiation ceased. AMD3100 protection from UV immunosuppression and skin cancer was associated with reduced mast cell infiltration into the skin, draining lymph nodes, and the tumor itself. Thus a major target of CXCR4 antagonism was the mast cell. Our results indicate that interfering with UV-induced CXCL12 by antagonizing CXCR4 significantly inhibits skin tumor development by blocking UV-induced effects on mast cells. Hence, the CXCR4-CXCL12 chemokine pathway is a novel therapeutic target in the prevention of UV-induced skin cancer.
    Matched MeSH terms: Mast Cells/metabolism; Mast Cells/radiation effects
  4. Puebla-Osorio N, Sarchio SNE, Ullrich SE, Byrne SN
    Methods Mol Biol, 2017;1627:213-222.
    PMID: 28836204 DOI: 10.1007/978-1-4939-7113-8_14
    Mast cells are part of the immune system and characteristically contain histamine- and heparin-rich basophilic granules. While these cells are usually associated with allergy and anaphylaxis, they also promote wound healing and angiogenesis and confer protection against pathogens. The presence of these cells is sometimes indicative of a poor prognosis, especially in skin cancer, pancreatic cancer, and lymphoma. Toluidine blue staining of acid-fast granules is an established method for the identification and quantification of mast cells. Generating detailed information on the location of mast cells within tissues is problematic using this technique and often requires serial sections from adjacent tissue to be separately stained with hematoxylin and eosin (H&E). Staining serial sections is not always possible, particularly if the sample is very small or rare. In such cases, a method of simultaneously identifying and localizing mast cells in a tissue would be advantageous. Toluidine blue and H&E are not commonly combined because H&E includes repetitive washes in water, which may affect the efficacy of the aqueous-soluble toluidine blue. We have developed and tested a novel staining technique that integrates toluidine blue between hematoxylin and eosin in one simple procedure. This protocol works on both frozen and formalin-fixed, paraffin-embedded tissue and readily allows for the identification of purple-stained mast cells against a clean H&E background. This facilitates a more accurate localization and proper counting of mast cells in normal and affected tissue.
    Matched MeSH terms: Mast Cells/metabolism*; Mast Cells/pathology*
  5. Soo KM, Tham CL, Khalid B, Basir R, Chee HY
    Trop Biomed, 2019 Dec 01;36(4):1027-1037.
    PMID: 33597472
    Dengue is a common infection, caused by dengue virus. There are four different dengue serotypes, with different capacity to cause severe dengue infections. Besides, secondary infections with heterologous serotypes, concurrent infections of multiple dengue serotypes may alter the severity of dengue infection. This study aims to compare the severity of single infection and concurrent infections of different combinations of dengue serotypes in-vitro. Human mast cells (HMC)-1.1 were infected with single and concurrent infections of multiple dengue serotypes. The infected HMC-1.1 supernatant was then added to human umbilical cord vascular endothelial cells (HUVEC) and severity of dengue infections was measured by the percentage of transendothelial electrical resistance (TEER). Levels of IL10, CXCL10 and sTRAIL in HMC-1.1 and IL-8, IL-10 and CXCL10 in HUVEC culture supernatants were measured by the ELISA assays. The result showed that the percentage of TEER values were significantly lower in single infections (p< 0.05), compared to concurrent infections on day 2 and 3, indicating that single infection increase endothelial permeability greater than concurrent infections. IL-8 showed moderate correlation with endothelial permeability (r > 0.4), indicating that IL-8 may be suitable as an in-vitro severity biomarker. In conclusion, this in-vitro model presented few similarities with regards to the conditions in dengue patients, suggesting that it could serve as a severity model to test for severity and levels of severity biomarkers upon different dengue virus infections.
    Matched MeSH terms: Mast Cells/virology
  6. Sinniah A, Yazid S, Flower RJ
    Front Pharmacol, 2017;8:827.
    PMID: 29184504 DOI: 10.3389/fphar.2017.00827
    The anti-allergic cromones were originally synthesized in the 1960s by Fisons Plc, and the first drug to emerge from this program, disodium cromoglycate was subsequently marketed for the treatment of asthma and other allergic conditions. Whilst early studies demonstrated that the ability of the cromones to prevent allergic reactions was due to their 'mast cell stabilizing' properties, the exact pharmacological mechanism by which this occurred, remained a mystery. Here, we briefly review the history of these drugs, recount some aspects of their pharmacology, and discuss two new explanations for their unique actions. We further suggest how these findings could be used to predict further uses for the cromones.
    Matched MeSH terms: Mast Cells
  7. Sanusi SY, Hallett KB
    J Dent Child (Chic), 2021 Jan 15;88(1):62-65.
    PMID: 33875055
    Mastocytosis is a heterogeneous disease of bone marrow origin, characterized by local or diffuse increased growth and accumulation of clonal mast cells in the skin and/or in internal organs. The skin is the organ most frequently involved, but others may be affected as well. The purpose of this article is to present the oral management of a child with urticaria pigmentosa/maculopapulous cutaneous mastocytosis requiring dental treatment under general anesthesia. The multidisciplinary team approach involving the relevant medical specialists is discussed to emphasize the significance of coordinated patient management.
    Matched MeSH terms: Mast Cells
  8. Abd Rani NZ, Kumolosasi E, Jasamai M, Jamal JA, Lam KW, Husain K
    BMC Complement Altern Med, 2019 Dec 11;19(1):361.
    PMID: 31829185 DOI: 10.1186/s12906-019-2776-1
    BACKGROUND: Moringa oleifera Lam. is a commonly used plant in herbal medicine and has various reported bioactivities such as antioxidant, antimicrobial, anticancer and antidiabetes. It is rich in nutrients and polyphenols. The plant also has been traditionally used for alleviating allergic conditions. This study was aimed to examine the anti-allergic activity of M. oleifera extracts and its isolated compounds.

    METHOD: M. oleifera leaves, seeds and pods were extracted with 80% of ethanol. Individual compounds were isolated using a column chromatographic technique and elucidated based on the nuclear magnetic resonance (NMR) and electrospray ionisation mass spectrometry (ESIMS) spectral data. The anti-allergic activity of the extracts, isolated compounds and ketotifen fumarate as a positive control was evaluated using rat basophilic leukaemia (RBL-2H3) cells for early and late phases of allergic reactions. The early phase was determined based on the inhibition of beta-hexosaminidase and histamine release; while the late phase was based on the inhibition of interleukin (IL-4) and tumour necrosis factor (TNF-α) release.

    RESULTS: Two new compounds; ethyl-(E)-undec-6-enoate (1) and 3,5,6-trihydroxy-2-(2,3,4,5,6-pentahydroxyphenyl)-4H-chromen-4-one (2) together with six known compounds; quercetin (3), kaempferol (4), β-sitosterol-3-O-glucoside (5), oleic acid (6), glucomoringin (7), 2,3,4-trihydroxybenzaldehyde (8) and stigmasterol (9) were isolated from M. oleifera extracts. All extracts and the isolated compounds inhibited mast cell degranulation by inhibiting beta-hexosaminidase and histamine release, as well as the release of IL-4 and TNF-α at varying levels compared with ketotifen fumarate.

    CONCLUSION: The study suggested that M. oleifera and its isolated compounds potentially have an anti-allergic activity by inhibiting both early and late phases of allergic reactions.

    Matched MeSH terms: Mast Cells/drug effects*
  9. Abd Rani NZ, Lam KW, Jalil J, Mohamad HF, Mat Ali MS, Husain K
    Molecules, 2021 Jan 28;26(3).
    PMID: 33525733 DOI: 10.3390/molecules26030695
    Phyllanthus amarus Schum. & Thonn. (Phyllanthaceae) is a medicinal plant that is commonly used to treat diseases such as asthma, diabetes, and anemia. This study aimed to examine the antiallergic activity of P. amarus extract and its compounds. The antiallergic activity was determined by measuring the concentration of allergy markers release from rat basophilic leukemia (RBL-2H3) cells with ketotifen fumarate as the positive control. As a result, P. amarus did not stabilize mast cell degranulation but exhibited antihistamine activity. The antihistamine activity was evaluated by conducting a competition radioligand binding assay on the histamine 1 receptor (H1R). Four compounds were identified from the high performance liquid chromatography (HPLC) analysis which were phyllanthin (1), hypophyllanthin (2), niranthin (3), and corilagin (4). To gain insights into the binding interactions of the most active compound hypophyllanthin (2), molecular docking was conducted and found that hypophyllanthin (2) exhibited favorable binding in the H1R binding site. In conclusion, P. amarus and hypophyllanthin (2) could potentially exhibit antiallergic activity by preventing the activation of the H1 receptor.
    Matched MeSH terms: Mast Cells/drug effects; Mast Cells/metabolism
  10. Abdulla MA, Khairul Anuar A, Khalifa S, Salmah I, Mohamad Nazmul HM, Suzainur KAR, et al.
    JUMMEC, 2002;7:135-141.
    Four calves from each group of purebred Kedah kelantan (KK), halfbred KK X Friesian, and quarterbred KK X Friesian were experimentally infested with Boophilus micropills larvae. Two calves from each genotype were injected, intramuscularly with antihistamine while the remaining two animals in each genotype received the same dose of antihistamine and dexamethasone. Dexamethasone combined anti-histamine treatment suppress tick resistance as manifested by the production of higher number of engorged female ticks, higher mean weight of replete ticks, mean weight of eggs and mean number of larvae hatched from 1 g of eggs. In anti-histamine treated animals there was no reduction of resistant in all animals as manifested by a few ticks were able to feed successfully. At 1, 2, and 3 hours post-larval attachment in anti-histamine and dexamethasone treated cattle there was complete ablation of the cellular infiltration in the dermis beneath the tick mouthparts, especially eosinophil and basophils. There was little destruction of tissue. However, in anti-histamine treated cattle there were more cellular infiltration and degranulation in the dermis. The cells infiltrating the dermis were mainly eosinophils followed by neutrophs, mast cells and basophils and some of these cells showed sign of degranulation. At 24 hours postlarval attachment, animals lTeated with anti-histamine and dexamethasone showed reduction of, cellular infiltration, degranulation, size of the epidermal lesion and tissue damage. The neutrophils were the predominant cells within the epidermal lesions. However, animals in anti-histamine treatment showed edema, more cellular infiltration and degranulation, and destruction of tissues as compared to antihistamine and dexamethasone treated animals. In anti-histamine treated cattle the epidermal lesions were obviously larger and the percentage of eosinophils and basophils were higher than those of antihistamine and dexamethasone treated animals. KEYWORDS: Kedah-Kelantan cattle, KK X Friesian callie, B. micropflls, dexamethasone, antihistamine, cellular response.
    Matched MeSH terms: Mast Cells
  11. Abdullah B, Hassan S, Sidek D, Jaafar H
    J Laryngol Otol, 2006 Jul;120(7):556-60.
    PMID: 16834804 DOI: 10.1017/S002221510
    INTRODUCTION: Otitis media with effusion (OME) is an inflammation of the middle ear in which a collection of liquid is present in the middle-ear space while the tympanic membrane is intact. The association between adenoid inflammation and OME has long been noted but the exact mechanism is still much debated. We studied the role of adenoid mast cells in the causation of OME.
    OBJECTIVE: To study the distribution and role of adenoid mast cells in the causation of OME.
    METHODOLOGY: A cross-sectional, prospective study was carried out in the otorhinolaryngologic clinic, department of otorhinolaryngology (ORL), Science University of Malaysia, from June 1999 to September 2001. A total number of 50 cases were studied. Twenty-five of these patients underwent adenoidectomy, while another 25 patients underwent adenoidectomy and myringotomy with ventilation tube insertion. The adenoid specimens from all patients were examined for the number of adenoid mast cells present, using light microscopy and toluidine blue as the staining agent. The results were analysed using SPSS version 10.0 computer software.
    RESULT: The population of adenoid mast cells in children with OME was significantly greater than that in children without OME (p=0.000).
    CONCLUSION: The increased number of adenoid mast cells in patients with OME suggests that inflammation may play a role in this condition.
    Matched MeSH terms: Mast Cells/pathology*
  12. Ji, Wei Tan
    MyJurnal
    Mast cells (MCs) play a crucial role in the pathogenesis of allergic diseases due to their hypersensitive reaction to non-harmful substances that elicit an allergic response. As such, by interrupting certain signalling proteins within the signalling pathway of a MC, an allergic response may be avoided or inhibited. Compounds that attenuate the release of mediators from MCs are known as MC stabilizers. These drugs are clinically used to prevent MC effector responses towards common allergens. Although commonly prescribed clinical MC stabilizers such as disodium cromoglycate and ketotifen fumarate were used in the preventative treatment of various allergic diseases, there still remains a need of advancement towards the discovery of new MC stabilizing drugs that are able to target specific signalling molecules in order to provide better treatment option against these diseases. Among these newly discovered potential MC stabilizers, much efforts have been given to the inhibition of vital upstream signalling molecules such as spleen tyrosine kinase as well as surface receptors such as the high-affinity IgE receptor (FcεRI) and stem cell factor receptor (KIT). A recent study also reported that linker for activation of T cells (LAT) may also be an excellent molecular target for inhibiting MC degranulation. Although in most cases the exact mode of action of these molecules is yet to be elucidated, all these compounds have shown MC inhibition. Therefore, they might have potential therapeutic use in the treatment of allergies and allergy related diseases where MCs are majorly involved. Thus, this mini review will focus on summarising the potential signalling molecules or receptors that have been targeted to inhibit MC degranulation, particularly those located in the upstream signalling pathway.
    Matched MeSH terms: Mast Cells
  13. Jaćević V, Wu Q, Nepovimova E, Kuča K
    Environ Toxicol Pharmacol, 2019 Oct;71:103221.
    PMID: 31365892 DOI: 10.1016/j.etap.2019.103221
    Our aim was to compare the protective efficacy of two different formulations of methylprednisolone in T-2 toxin-induced cardiomyopathy. Methylprednisolone (soluble form, Lemod-solu® and/or depot form, Lemod-depo®, a total single dose of 40 mg/kg im) was given immediately after T-2 toxin (1 LD50 0.23 mg/kg sc). The myocardial tissue samples were examinated by using histopathology, semiquantitative and imaging analyses on day 1, 7, 14, 21, 28 and 60 of the study. Therapeutic application of Lemod-solu® significantly decreased the intensity of myocardial degeneration and haemorrhages, distribution of glycogen granules in the endo- and perimysium, a total number of mast cells and the degree of their degranulation was in correlation with the reversible heart structural lesions (p 
    Matched MeSH terms: Mast Cells
  14. Jaćević V, Wu Q, Nepovimova E, Kuča K
    Food Chem Toxicol, 2020 Jan 22.
    PMID: 31981685 DOI: 10.1016/j.fct.2020.111138
    T-2 toxin, A trichothecenes mycotoxin, is immunotoxic to animals and humans. Although it is highly cardiotoxic, the pathogenesis of cardiomyopathy caused by T-2 toxin is not entirely clear. Hence, in our research, cardiomyopathy was induced by a single injection of T-2 mycotoxin (0.23 mg/kg s.c., 1 LD50.) to Wistar rats. The cardiac tissue was carefully examinated by using basic histopathology, semiquantitative (tissue grading score scales) and imaging (a total number of mast cells - MCs) analyses on days 1, 7, 14, 21, 28 and 60 of the study. The most intensive myocardial alterations (cardiac damage score, CDS = 4.20-4.40), irregular glycogen distribution (glycogen distribution score, GDS = 4.07-4.17), haemorrhagic foci (vascular damage score, VDS = 4.57-4.90), diffuse accumulation and degranulation of MCs were observed on day 28 and 60 after treatment (p 
    Matched MeSH terms: Mast Cells
  15. Byrne SN, Sarchio SN
    Oncoimmunology, 2014 Jan 01;3(1):e27562.
    PMID: 24744978
    Sunlight causes skin cancer by directly damaging DNA as well as by suppressing antitumor immune responses. A major mechanism whereby sunlight exerts immunosuppressive effects is by modulating the migration of chemokine (C-X-C motif) receptor 4 (CXCR4)-expressing dermal mast cells into and away from the skin. We have demonstrated the importance of this by showing that the systemic administration of the CXCR4 antagonist AMD3100 prevents sunlight-induced immunosuppression as well as the consequent carcinogenic response. Our results highlight the therapeutic potential of antagonizing CXCR4 signaling, especially in individuals who are at high risk of developing skin cancer.
    Matched MeSH terms: Mast Cells
  16. Wong KT, Shamsol S
    J Cutan Pathol, 1999 Jan;26(1):13-6.
    PMID: 10189239
    The association of mast cells with typical lesions of Kimura's disease was investigated by quantitative methods after immunohistochemical staining for Factor VIII-related antigen and counterstaining with toluidine blue. Formalin-fixed, paraffin-embedded, tissue sections from 9 confirmed cases of Kimura's disease were examined after staining to estimate mast cell and blood vessel densities by counting 100 random fields under oil immersion. There was a statistically significant increase of both mast cells and blood vessels in Kimura's disease (p<0.01) compared with normal skin and reactive lymph node controls. However, as far as the individual Kimura's disease lesion is concerned, there was generally no correlation between areas with mast cell increase and the degree of vascularity. Moreover, when lesions of less than 1 year's duration were compared with older lesions, there appeared to be a relative decrease in mast cells and a concomitant increase in vascularity in the latter. These results confirmed that mast cells are associated with Kimura's disease, and suggest that they may be involved in its early pathogenesis, although its possible role in angiogenesis may not be direct.
    Matched MeSH terms: Mast Cells/cytology; Mast Cells/pathology*; Mast Cells/chemistry
  17. Yong PYA, Yip AJW, Islam F, Hong HJ, Teh YE, Tham CL, et al.
    BMC Complement Med Ther, 2023 Sep 04;23(1):307.
    PMID: 37667314 DOI: 10.1186/s12906-023-04129-y
    BACKGROUND: Allergy is an inflammatory disorder affecting around 20% of the global population. The adverse effects of current conventional treatments give rise to the increased popularity of using natural food products as complementary and alternative medicine against allergic diseases. Stingless bee honey, commonly known as Kelulut honey (KH) in Malaysia, has been used locally as a traditional remedy to relieve cough and asthma. This study evaluated the anti-allergic potential of KH collected from four different botanical sources on phorbol ester 12-myristate-3-acetate and calcium ionophore-activated human mast cells.

    METHODS: The present study examined the inhibitory effects of all collected honey on the release of selected inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, IL-8, histamine, and β-hexosaminidase in an activated HMC. Besides that, all honey's total phenolic content (TPC) was also examined, followed by using liquid chromatography with tandem mass spectrometry (LC-MS/MS) to identify the phytochemicals in the honey. Further examination of the identified phytochemicals on their potential interaction with selected signaling molecules in an activated mast cell was conducted using computational methods.

    RESULTS: The results indicated that there were significant inhibitory effects on all selected inflammatory mediators' release by KH sourced from bamboo (BH) and rubber tree (RH) at 0.5% and 1%, but not KH sourced from mango (AH) and noni (EH). BH and RH were found to have higher TPC values and were rich in their phytochemical profiles based on the LC-MS/MS results. Computational studies were employed to determine the possible molecular target of KH through molecular docking using HADDOCK and PRODIGY web servers.

    CONCLUSIONS: In short, the results indicated that KH possesses anti-allergic effects towards an activated HMC, possibly by targeting downstream MAPKs. However, their anti-allergic effects may vary according to their botanical sources. Nevertheless, the present study has provided insight into the potential application of stingless bee honey as a complementary and alternative medicine to treat various allergic diseases.

    Matched MeSH terms: Mast Cells
  18. Tan JW, Israf DA, Md Hashim NF, Cheah YK, Harith HH, Shaari K, et al.
    Biochem Pharmacol, 2017 Nov 15;144:132-148.
    PMID: 28813645 DOI: 10.1016/j.bcp.2017.08.010
    Mast cells play a central role in the pathogenesis of allergic reaction. Activation of mast cells by antigens is strictly dependent on the influx of extracellular calcium that involves a complex interaction between signalling molecules located within the cells. We have previously reported that tHGA, an active compound originally isolated from a local shrub known as Melicope ptelefolia, prevented IgE-mediated mast cell activation and passive systemic anaphylaxis by suppressing the release of interleukin-4 (IL-4) and tumour necrosis factor (TNF)-α from activated rat basophilic leukaemia (RBL)-2H3 cells. However, the mechanism of action (MOA) as well as the molecular target underlying the mast cell stabilising effect of tHGA has not been previously investigated. In this study, DNP-IgE-sensitised RBL-2H3 cells were pre-treated with tHGA before challenged with DNP-BSA. To dissect the MOA of tHGA in IgE-mediated mast cell activation, the effect of tHGA on the transcription of IL-4 and TNF-α mRNA was determined using Real Time-Polymerase Chain Reaction (qPCR) followed by Calcium Influx Assay to confirm the involvement of calcium in the activation of mast cells. The protein lysates were analysed by using Western Blot to determine the effect of tHGA on various important signalling molecules in the LAT-PLCγ-MAPK and PI3K-NFκB pathways. In order to identify the molecular target of tHGA in IgE-mediated mast cell activation, the LAT and LAT2 genes in RBL-2H3 cells were knocked-down by using RNA interference to establish a LAT/LAT2 competition model. The results showed that tHGA inhibited the transcription of IL-4 and TNF-α as a result of the suppression of calcium influx in activated RBL-2H3 cells. The results from Western Blot revealed that tHGA primarily inhibited the LAT-PLCγ-MAPK pathway with partial inhibition on the PI3K-p65 pathway without affecting Syk. The results from RNAi further demonstrated that tHGA failed to inhibit the release of mediators associated with mast cell degranulation under the LAT/LAT2 competition model in the absence of LAT. Collectively, this study concluded that the molecular target of tHGA could be LAT and may provide a basis for the development of a mast cell stabiliser which targets LAT.
    Matched MeSH terms: Mast Cells/drug effects*; Mast Cells/metabolism*
  19. Tan JW, Wan Zahidi NF, Kow ASF, Soo KM, Shaari K, Israf DA, et al.
    Biosci Rep, 2019 06 28;39(6).
    PMID: 31110077 DOI: 10.1042/BSR20181273
    Mast cells (MCs), a type of immune effector cell, have recently become recognized for their ability to cause vascular leakage during dengue virus (DENV) infection. Although MC stabilizers have been reported to attenuate DENV induced infection in animal studies, there are limited in vitro studies on the use of MC stabilizers against DENV induced MC degranulation. 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA) has been reported to be a potential MC stabilizer by inhibiting IgE-mediated MC activation in both cellular and animal models. The present study aims to establish an in vitro model of DENV3-induced RBL-2H3 cells using ketotifen fumarate as a control drug, as well as to determine the effect of tHGA on the release of MC mediators upon DENV infection. Our results demonstrated that the optimal multiplicities of infection (MOI) were 0.4 × 10-2 and 0.8 × 10-2 focus forming units (FFU)/cell. Ketotifen fumarate was proven to attenuate DENV3-induced RBL-2H3 cells degranulation in this in vitro model. In contrast, tHGA was unable to attenuate the release of both β-hexosaminidase and tumor necrosis factor (TNF)-α. Nonetheless, our study has successfully established an in vitro model of DENV3-induced RBL-2H3 cells, which might be useful for the screening of potential MC stabilizers for anti-dengue therapies.
    Matched MeSH terms: Mast Cells/drug effects*; Mast Cells/immunology; Mast Cells/physiology
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