Anti-allergic effects of Lycopus lucidus on mast cell-mediated allergy model

The current study characterizes the mechanism by which the aqueous extract of Lycopus lucidus Turcz. (Labiatae) (LAE) decreases mast cell-mediated immediate-type allergic reaction. The immediate-type allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. LAE has been used as a traditional medicine in Korea and is known to have an anti-inflammatory effect. However, its specific mechanism of action is still unknown. LAE was anally administered to mice for high and fast absorption. LAE inhibited compound 48/80-induced systemic reactions in mice. LAE decreased the local allergic reaction, passive cutaneous anaphylaxis, activated by anti-dinitrophenyl (DNP) IgE antibody. LAE dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, LAE decreased the secretion of TNF-alpha and IL-6 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated human mast cells. The inhibitory effect of LAE on the pro-inflammatory cytokine was p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) dependent. LAE attenuated PMA plus A23187-induced degradation of IkappaBalpha and nuclear translocation of NF-kappaB, and specifically blocked activation of p38 MAPK, but not that of c-jun N-terminal kinase and extracellular signal-regulated kinase. Our findings provide evidence that LAE inhibits mast cell-derived immediate-type allergic reactions and involvement of pro-inflammatory cytokines, p38 MAPK, and NF-kappaB in these effects.     

Inhibition of anaphylaxis like reaction and mast cell activation by Sitagliptin

Mast cells stimulation activates degranulation process resulting in releasing of mediators, such as histamine. In this study, the effect of aqueous extract of sitagliptin, a selective dipeptidylpeptidase-4 inhibitor, on the mast cell-mediated allergic response was studied with the possible mechanisms of action, focusing on the histamine release and pro-inflammatory cytokine secretion in mast cells. Sitagliptin produced dose dependent inhibition in compound 48/80-induced systemic reactions. In addition, sitagliptin attenuated IgE-mediated skin allergic reaction. Sitagliptin dose-dependently reduced compound 48/80- and IgE-induced histamine release from mast cells. Sitagliptin decreased the secretion of pro-inflammatory cytokines, tumor necrosis factor-α, in mast cells. So, the finding of this study provides evidence that sitagliptin inhibits mast cell derived allergic reactions, and involvement of pro-inflammatory cytokine secretion in such effects.     

Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells.

The discovery of drugs for the treatment of inflammatory allergic diseases such as, asthma, allergic rhinitis, and sinusitis is a very important subject in human health. Gallic acid (3,4,5-trihydroxybenzoic acid), a polyphenyl natural products from gallnut and green tea, is known to have anti-oxidant, anti-inflammatory, anti-microbial, and radical scavenging activities. The aim of the present study was to elucidate whether gallic acid modulates the inflammatory allergic reaction and to study its possible mechanisms of action. Gallic acid attenuated compound 48/80- or immunoglobulin E (IgE)-induced histamine release from mast cells. The inhibitory effect of gallic acid on the histamine release was mediated by the modulation of cAMP and intracellular calcium. Gallic acid decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated pro-inflammatory cytokine gene expression and production such as TNF-alpha and IL-6 in human mast cells. The inhibitory effect of gallic acid on the pro-inflammatory cytokine was nuclear factor-kappaB and p38 mitogen-activated protein kinase dependent. In addition, gallic acid inhibited compound 48/80-induced systemic allergic reaction and IgE-mediated local allergic reaction. The inhibitory activity of gallic acid on the allergic reaction and histamine release was found to be similar with disodium cromoglycate. Our findings provide evidence that gallic acid inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression, and suggest the mechanisms of action. Furthermore, in vivo and in vitro anti-allergic effect of gallic acid suggests a possible therapeutic application of this agent in inflammatory allergic diseases.     

The anti-anaphylactic effect of the gall of Rhus javanica is mediated through inhibition of histamine release and inflammatory cytokine secretion

The immediate-type allergic reaction (anaphylaxis) is involved in many allergic diseases such as asthma, allergic rhinitis and sinusitis. We investigated the effect of the gall of Rhus javanica (GRJ) on the model of the immediate-type allergic reaction, and studied its possible mechanisms. GRJ inhibited compound 48/80-induced systemic reactions in mice. GRJ attenuated immunoglobulin (Ig) E-mediated local allergic reactions. In addition, GRJ dose dependently decreased histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. The decreasing effect of GRJ on the histamine release was mediated by the modulation of cAMP and [Ca2+]i in mast cells. Furthermore, GRJ decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated TNF-alpha and IL-6 secretion in human mast cells. The inhibitory effect of GRJ on the pro-inflammatory cytokine was c-Jun N-terminal kinase and nuclear factor-kappaB dependent. Our findings provide evidence that GRJ inhibits mast cell-derived immediate-type allergic reactions, and suggest the possible mechanisms of action.     

Suppression of mast cell-mediated allergic reaction by Amomum xanthiodes.

The mast cell-mediated immediate-type allergic reaction is involved in many allergic diseases such as asthma, allergic rhinitis and sinusitis. Stimulation of mast cells starts the process of degranulation resulting in release of mediators such as histamine and an array of inflammatory cytokines. In this report, we investigated the effect of aqueous extract of Amomum xanthiodes (Zingiberaceae) (AXE) on the mast cell-mediated allergy model and studied its possible mechanisms of action. AXE inhibited compound 48/80-induced systemic reactions and serum histamine release in mice. AXE decreased immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis reaction. AXE reduced histamine release and intracellular calcium from rat peritoneal mast cells activated by compound 48/80. Furthermore, AXE decreased the activation of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase and c-jun N-terminal kinase, and downstream tumor necrosis factor (TNF)-alpha production in phorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated human mast cells. Our findings provide evidence that AXE inhibits mast cell-derived allergic reactions, and that intracellular calcium, TNF-alpha, and p38 MAPK are involved in these effects.     

Mosla dianthera inhibits mast cell-mediated allergic reactions through the inhibition of histamine release and inflammatory cytokine production

In this study, we investigated the effect of the aqueous extract of Mosla dianthera (Maxim.) (AEMD) on the mast cell-mediated allergy model and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as asthma, sinusitis and rheumatoid arthritis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. AEMD inhibited compound 48/80-induced systemic reactions in mice. AEMD decreased immunoglobulin E-mediated local allergic reactions, passive cutaneous anaphylaxis. AEMD attenuated intracellular calcium level and release of histamine from rat peritoneal mast cells activated by compound 48/80. Furthermore, AEMD attenuated the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-alpha, IL-8 and IL-6 secretion in human mast cells. The inhibitory effect of AEMD on the pro-inflammatory cytokines was nuclear factor-kappaB (NF-kappaB) dependent. AEMD decreased PMA and A23187-induced degradation of IkappaBalpha and nuclear translocation of NF-kappaB. Our findings provide evidence that AEMD inhibits mast cell-derived immediate-type allergic reactions and involvement of pro-inflammatory cytokines and NF-kappaB in these effects.     

中药制剂苓槐丸提取物对小鼠过敏性皮炎的治疗作用及机制研究

目的研究中药制剂苓槐丸对过敏性皮炎的治疗作用及机制。方法制备苓槐丸甲醇提取物（MELH）,观察其对过敏性皮炎模型鼠耳肿胀程度及炎症因子释放的影响;而后,检测MELH 对肥大细胞RBL鄄2H3 脱粒作用及细胞信号通路的影响。结果MELH 可有效抑制过敏性皮炎模型鼠耳炎症性肿大（P 〈0. 05）,及抑制鼠耳组织中IFN-γ和TNF-α水平升高（P 〈0. 05）。MELH 可剂量依赖性抑制佛波酯（PMA）和钙离子载体（A23187）联合引起的RBL鄄2H3 细胞的组胺释放（P〈0. 05）和p38 MAPK 磷酸化。结论MELH 通过抑制T 细胞炎症因子的释放、肥大细胞脱粒作用及p38 MAPK 通路的活化,阻止T细胞向Th1免疫偏离,总体说苓槐丸可起到明显的抗过敏性皮炎作用。     

Perfluorooctanoic acid induces mast cell-mediated allergic inflammation by the release of histamine and inflammatory mediators

Perfluorooctanoic acid (PFOA) has unique physical and chemical characteristics, water and oil repellency, thermal stability, and surfactant properties. PFOA has been regularly found in the blood of animals and humans worldwide, and has become an increasing concern because of its adverse effects in immune system. However, the role of PFOA in the allergic inflammation is not well-known. To further extend the immunotoxicity of PFOA, we examined the role of PFOA on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. PFOA dose- and time-dependently increased histamine release from mast cells and serum histamine by the induction of intracellular calcium. PFOA exacerbated the IgE-dependent local allergic reaction in the mouse allergy model. PFOA induced gene expression of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 in mast cells. The inducing effect of PFOA on the pro-inflammatory cytokines was nuclear factor-κB, p38 mitogen-activated protein kinase, and caspase-1 dependent. Furthermore, the activation of cyclooxygenase-2 by PFOA suggests the induction of allergic inflammatory mediators by the PFOA. Our findings provide evidence that PFOA, the known immunotoxic agent, induces mast cell-derived allergic inflammatory reactions by histamine release and expression of pro-inflammatory cytokines.     

Chrysin suppresses mast cell-mediated allergic inflammation: involvement of calcium, caspase-1 and nuclear factor-κB

A great number of people are suffering from allergic inflammatory diseases such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid contained in propolis, blue passion flower, and fruits. Several studies reported that chrysin has beneficial effects including anti-tumor and anti-oxidant activities. The aim of the present study was to elucidate whether chrysin modulates the allergic inflammatory reaction and to study its possible mechanisms of action using mast cell-based in vitro and in vivo models. Chrysin inhibited immediate-type systemic hypersensitivity and serum histamine release. Chrysin attenuated immunoglobulin E-mediated local anaphylaxis. These inhibitory effects of chrysin on the systemic and local allergic reaction were more potent than cromolyn, a known anti-allergic drug. Chrysin reduced histamine release from mast cells. The inhibitory effect of chrysin on the histamine release was mediated by the modulation of intracellular calcium. In addition, chrysin decreased gene expression of pro-inflammatory cytokines such as, tumor necrosis factor-α, IL (interleukin)-1β, IL-4, and IL-6 in mast cells. The inhibitory effect of chrysin on the pro-inflammatory cytokine was nuclear factor-κB and caspase-1 dependent. Our findings provide evidence that chrysin inhibits mast cell-derived allergic inflammatory reactions by blocking histamine release and pro-inflammatory cytokine expression, and suggest the mechanisms of action. Furthermore, in vivo and in vitro anti-allergic inflammatory effect of chrysin suggests a possible therapeutic application of this agent in allergic inflammatory diseases.     

Anti-inflammatory effect of leaves of Eriobotrya japonica correlating with attenuation of p38 MAPK, ERK, and NF-κB activation in mast cells

Mast cell-mediated allergic inflammation is involved in many diseases such as asthma and sinusitis. Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 with immune regulatory properties. In the present study, we investigate the effect an unspecified aqueous extract from leaves of Eriobotrya japonica Lindl. (Rosaceae) (LEJL) on the expression of pro-inflammatory cytokines and its possible mechanisms of action in human mast cells (HMC-1). LEJL dose-dependently inhibited phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 (PMACI)-induced gene expression and secretion of TNF-α, IL-6, and IL-8. LEJL attenuated PMACI-induced activation of nuclear factor (NF)-κB, and specifically blocked activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) but not that of c-jun N-terminal kinase. The inhibitory effect of LEJL on the pro-inflammatory cytokines was likely NF-κB, p38 MAPK, and ERK dependent. Our in vitro studies provide evidence that LEJL might contribute to the treatment of mast cell-derived allergic inflammatory diseases.     

Anti-allergic effects of nilotinib on mast cell-mediated anaphylaxis like reactions

Nilotinib is a new orally bioavailable potent tyrosine kinase inhibitor that is used for the treatment of BCR-ABL-positive chronic myelogenous leukemia. However, its effect on mast cell-mediated anaphylactic reaction is still not known. The present study aimed to investigate the effect of nilotinib on the anaphylactic allergic reaction and study its possible mechanism(s) of action. Nilotinib administration prevented systemic anaphylaxis in mice, mediated by compound 48/80, in a dose- and time-dependent manner. Also, nilotinib significantly inhibited (P<0.05) allergic paw edema in rats. Furthermore, nilotinib significantly decreased (P<0.05) the IgE-mediated passive cutaneous anaphylaxis in a dose dependent manner. In addition, nilotinib dose-dependently reduced histamine release from the rat peritoneal mast cells activated either by compound 48/80 or by ovalbumin. Moreover, nilotinib attenuated the secretion of pro-inflammatory cytokine, tumor necrosis factor (TNF)-α expression in the rat peritoneal mast cells. These findings provide evidence that nilotinib inhibits mast cell-derived immediate-type allergic reactions and so it could be a candidate as an anti-allergic agent.     

Inhibition of immediate allergic reactions by ethanol extract from Plumbago zeylanica stems

The antiallergic properties of the 70% ethanol extract from Plumbago zeylanica stems (EPZ) were investigated in the present study. The extract (500, 1000 mg/kg, p.o.) dose-dependently inhibited systemic anaphylactic shock induced by compound 48/80 in mice, reduced homologous passive cutaneous anaphylaxis and skin reactions induced by histamine or serotonin in rats, significant differences were observed at the dose of 1000 mg/kg. In vitro, EPZ (5, 20, 50 microg/ml) concentration-dependently reduced histamine release from rat peritoneal mast cells caused by compound 48/80 and antigen. EPZ (50 microg/ml) markedly increased intracellular cAMP content of rat mast cells. These findings demonstrate that EPZ inhibits mast cell-dependent immediate allergic reactions, which is probably mediated by reducing the release of mediators such as histamine from mast cells via elevating intracellular cAMP level and weakening the inflammatory action of mediators.     

Regulation of IL-1-induced selective IL-6 release from human mast cells and inhibition by quercetin

Mast cells are involved in allergic reactions, but also in innate immunity and inflammation. Crosslinkage of mast cell Fc immunoglobulin E receptors (FcvarepsilonRI) by multivalent antigen triggers secretion of granule-stored mediators, as well as de novo synthesis of cytokines, including interleukin (IL)-6. We showed recently that the proinflammatory cytokine IL-1 stimulates human leukemic mast cells (HMC-1) and human umbilical cord blood-derived cultured mast cells (hCBMCs) to release newly synthesized IL-6 without tryptase in the absence of degranulation. Here, we investigated several signal-transduction pathways activated by IL-1 leading to IL-6 production by HMC-1 and hCBMCs. We also investigated the effect of the flavonol quercetin that was recently shown to strongly inhibit IL-6 secretion in response to allergic stimulation from hCBMCs.IL-1 stimulated p38, but did not activate extracellular signal-regulated kinase (ERK) or c-jun N-terminal kinase (JNK); it also did not activate protein kinase C (PKC) isozymes alpha, beta, mu and zeta, except for PKC-theta, which was phosphorylated. The p38 inhibitor SB203580 and the PKC inhibitors Calphostin C and G?6976 completely inhibited IL-1-induced IL-6 production. Quercetin 1-100 microM inhibited IL-1-induced IL-6 secretion, p38 and PKC-theta phosphorylation in a dose-dependent manner. These results indicate that IL-1-stimulated IL-6 production from human mast cells is regulated by biochemical pathways distinct from IgE-induced degranulation and that quercetin can block both IL-6 secretion and two key signal transduction steps involved.     

Galangin attenuates mast cell-mediated allergic inflammation

A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. In this study, we investigated anti-allergic inflammatory effect of galangin and underlying mechanisms of action using in vitro and in vivo models. Galangin inhibited histamine release by the reduction of intracellular calcium in phorbol 12-mystate 13-acetate plus calcium ionophore A23187-stimulated human mast cells (HMC-1). Galangin decreased expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8. The inhibitory effect of galangin on theses pro-inflammatory cytokines was related with c-Jun N-terminal kinases, and p38 mitogen-activated protein kinase, nuclear factor-κB, and caspase-1. Furthermore, galangin attenuated IgE-mediated passive cutaneous anaphylaxis and the expression of histamine receptor 1 at the inflamed tissue. The inhibitory effects of galangin were more potent than cromolyn, a known anti-allergic drug. Our results showed that galangin down-regulates mast cell-derived allergic inflammatory reactions by blocking histamine release and expression of pro-inflammatory cytokines. In light of in vitro and in vivo anti-allergic inflammatory effects, galangin could be a beneficial anti-allergic inflammatory agent.     

Corticotropin-releasing hormone induces vascular endothelial growth factor release from human mast cells via the cAMP/protein kinase A/p38 mitogen-activated protein kinase pathway

Mast cells are involved in allergic reactions but also in innate immunity and inflammation. Corticotropin-releasing hormone (CRH), the key regulator of the hypothalamic-pituitary-adrenal axis, also has proinflammatory effects, apparently through mast cells. We showed recently that CRH selectively stimulates human leukemic mast cells and human umbilical cord blood-derived mast cells to release newly synthesized vascular endothelial growth factor (VEGF) without release of either preformed mediators or cytokines. This effect was mediated through the activation of CRH receptor-1 and adenylate cyclase with increased intracellular cAMP. However, the precise mechanism by which CRH induces VEGF secretion has not yet been defined. Here, we show that CRH-induced VEGF release was dose-dependently inhibited by the specific protein kinase A inhibitor N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H89) or the p38 mitogen-activated protein kinase (MAPK) inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) but not by the specific inhibitor 2'-amino-3'-methoxyflavone (PD98059) of mitogen-activated protein kinase kinase, the upstream kinase of the extracellular signal-regulated protein kinase (ERK) or the c-Jun N-terminal kinase (JNK) inhibitor 1,9-pyrazoloanthrone anthra-(1,9-cd)pyrazol-6(2H)-one (SP600125). Furthermore, CRH significantly increased protein kinase A activity, which could be mimicked by the cell-permeable cAMP analog 8-bromo-cAMP, and was blocked by H89 or the adenylate cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purine-6-amine (SQ22536). CRH also induced rapid phosphorylation of p38 MAPK, which was mimicked by 8-bromo-cAMP and was inhibited by H89 or SB203580. CRH did not stimulate ERK or JNK phosphorylation and did not increase intracellular calcium levels. These results indicate that CRH induces VEGF release in human mast cells via selective activation of the cAMP/protein kinase A/p38 MAPK signaling pathway, thereby providing further insight into the molecular mechanism of how CRH affects the release of a key proinflammatory mediator.     

Inhibitor of p42/44 mitogen-activated protein kinase, but not p38 MAPK, attenuated antigen challenge of guinea pig airways in vitro

Upon cross-linking of the high-affinity IgE receptors on mast cells, a family of mitogen-activated protein kinases (MAPKs) is activated. The present study examined the effects of p42/44 MAPK kinase inhibitor U0126 and p38 MAPK inhibitors SB220025 and PD169316 on ovalbumin (OVA)-induced anaphylactic contraction of isolated guinea pig bronchi and release of histamine and peptidoleukotrienes from lung fragments. Guinea pigs were actively sensitized by OVA. OVA induced anaphylactic bronchial contractions, and release of histamine and peptidoleukotrienes from lung fragments. U0126 (0.3-30 microM), but not SB220025 and PD169316 (3-30 microM), slightly suppressed peak OVA-induced bronchial contraction but markedly reduced anaphylactical contraction over a 50-min period in a dose-dependent manner. U0126 did not inhibit bronchial contractions induced by KCl, histamine or leukotriene D4. U0126 produced a slight reduction in OVA-induced release of histamine but a significant inhibition on the release of peptidoleukotrienes from lung fragments. Exogenous arachidonic acid-induced release of peptidoleukotrienes was not blocked by U0126. SB220025 and PD169316 had no effect on OVA-induced release of histamine and peptidoleukotrienes. Our data indicate that inhibitor of p42/44 MAPK kinase, but not p38 MAPK, can reduce antigen-induced release of peptidoleukotrienes leading to a rapid resolution of anaphylactic bronchial contraction, and may have therapeutic potential for allergic asthma.     

Inhibition of anaphylaxis-like reaction and mast cell activation by water extract from the fruiting body of Phellinus linteus

Mast cell-mediated anaphylactic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. Phellinus linteus has been used as a traditional herb medicine in oriental countries and is known to have anti-tumor, immunomodulatory, anti-inflammatory, and anti-allergic activities. However, roles of Phellinus linteus in the mast cell-mediated anaphylactic reactions have not fully been examined. In the present study, we have investigated the effects of water extract from the fruiting body of Phellinus linteus (WEPL) on mast cell-mediated anaphylaxis-like reactions. Oral administration of WEPL inhibited the compound 48/80-induced systemic anaphylaxis-like reaction and ear swelling response. WEPL also inhibited the anti-dinitrophenyl (DNP) IgE-mediated passive systemic and cutaneous anaphylaxis. WEPL had no cytotoxicity on rat peritoneal mast cells (RPMC). WEPL dose-dependently reduced histamine release from RPMC activated by compound 48/80 or anti-DNP IgE. Moreover, WEPL decreased the compound 48/80-induced calcium uptake into RPMC. Furthermore, WEPL increased the level of intracellular cAMP and significantly inhibited the compound 48/80-induced cAMP reduction in RPMC. These results suggest that WEPL may serve as an effective therapeutic agent for allergic diseases.     

Anti-allergic effects of Teucrium japonicum on mast cell-mediated allergy model

The mast cell-mediated immediate-type allergic reaction is involved in many allergic diseases such as asthma, allergic rhinitis, and sinusitis. Stimulation of mast cells starts the process of degranulation resulting in release of mediators such as histamine and an array of inflammatory cytokines. In this report, we investigated the effect of aqueous extract of Teucrium japonicum Houttuyn (Labiatae) (AXTJ) on the mast cell-mediated allergy model and studied its possible mechanisms of action. AXTJ inhibited compound 48/80-induced systemic reactions and serum histamine release in mice. AXTJ decreased immunoglobulin E-mediated passive cutaneous anaphylaxis reaction. AXTJ reduced histamine release and intracellular calcium from rat peritoneal mast cells activated by compound 48/80. In addition, AXTJ attenuated activation of nuclear factor (NF)-κB, and downstream tumor necrosis factor (TNF)-α expression in phorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated human mast cells. Our findings provide evidence that AXTJ inhibits mast cell-derived allergic reactions and involvement of intracellular calcium, TNF-α, and NF-κB in these effects.     

The regulatory effect of SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-l]benzenesulfonamide) on stem cell factor induced migration of mast cells

SC-236, (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-]benzenesulfonamide; C(16)H(11)ClF(3)N(3)O(2)S), is a highly selective cyclooxygenase (COX)-2 inhibitor. Recently, there have been reports that SC-236 protects against cartilage damage in addition to reducing inflammation and pain in osteoarthritis. However, the mechanism involved in the inflammatory allergic reaction has not been examined. Mast cells accumulation can be related to inflammatory conditions, including allergic rhinitis, asthma, and rheumatoid arthritis. The aim of the present study is to investigate the effects of SC-236 on stem cell factor (SCF)-induced migration, morphological alteration, and cytokine production of rat peritoneal mast cells (RPMCs). We observed that SCF significantly induced the migration and morphological alteration. The ability of SCF to enhance migration and morphological alteration was abolished by treatment with SC-236. In addition, production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and vascular endothelial growth factor (VEGF) production induced by SCF was significantly inhibited by treatment with SC-236. Previous work has demonstrated that SCF-induced migration and cytokine production of mast cells require p38 MAPK activation. We also showed that SC-236 suppresses the SCF-induced p38 MAPK activation in RPMCs. These data suggest that SC-236 inhibits migration and cytokine production through suppression of p38 MAPK activation. These results provided new insight into the pharmacological actions of SC-236 and its potential therapeutic role in the treatment of inflammatory allergic diseases.