雷公藤多苷对人支气管上皮细胞16HBE凋亡和炎症因子释放的影响

目的 研究雷公藤多苷对屋尘螨抗原Derp1诱导的人支气管上皮细胞16HBE凋亡和炎症因子释放的影响。方法 人支气管上皮细胞16HBE分成对照组、Derp1组（屋尘螨抗原Derp1处理）、实验-5μg·mL^-1组(5μg·mL^-1雷公藤多苷和屋尘螨抗原Derp1处理)、实验-10μg·mL^-1组(10μg·mL^-1雷公藤多苷和屋尘螨抗原Derp1处理)、实验-10μg·mL^-1+pcDNA组(转染pcDNA,10μg·mL^-1雷公藤多苷和屋尘螨抗原Derp1处理)、实验-10μg·mL^-1+pcDNA-高迁移率族蛋白B1（HMGB1）组(转染pcDNA-HMGB1,10μg·mL^-1雷公藤多苷和屋尘螨抗原Derp1处理)。用蛋白质印迹法检测HMGB1、B细胞淋巴瘤/白血病-2（Bcl-2）、Bcl-2相关X蛋白（Bax）表达,用流式细胞术检测细胞凋亡,用酶联免疫吸附法检测培养液上清液中白细胞介素-6（IL-6）、肿...     

屋尘螨变应原结膜激发试验的影响因素分析

目的通过对屋尘螨变应原结膜激发试验（CPT）的主要影响因素分析,探讨进行临床评估屋尘螨变应原CPT结果时需排除哪些影响因素。方法选择2008年1月至2009年12月就诊的符合变应性鼻炎、结膜炎和（或）支气管哮喘诊断患者357例,所有入选者均进行屋尘螨变应原CPT,采用北京协和医院眼结膜激发试验评估标准分别记录,并分别记录性别、年龄、受累器官、病程、受试季节等影响疾病状态的因素,同时进行血清屋尘螨特异性免疫球蛋白E（d1—sIgE）检测。结果屋尘螨变应原CPT结果只与血清d1-sIgE相关（r=0．4722,P〈0．05）;而与受试季节、性别、年龄、病程、靶器官等因素无相关性（P〉0．05）。结论屋尘螨变应原CPT不受受试季节、性别、年龄、病程、靶器官等因素的影响,在临床评估屋尘螨变应原CPT结果工作中无须考虑这些因素的影响。     

屋尘螨变应原结膜激发试验在上下气道变态反应性疾病的临床比较

目的比较在上、下气道变态反应性疾病患者中屋尘螨变应原结膜激发试验（CPT）结果的差异,为在下气道变态反应性疾病诊断中屋尘螨变应原结膜激发试验的临床应用提供依据。方法选择2006至2008年在我科就诊的符合变应性鼻炎、结膜炎和（或）支气管哮喘诊断的患者178例,分为3组：单纯支气管哮喘组45例、支气管哮喘＋变应性鼻炎和（或）结膜炎组50例、变应性鼻炎和（或）结膜炎组83例。所有入选者均进行屋尘螨变应原结膜激发试验,采用北京协和医院眼结膜激发试验评估标准分别记录,同时进行屋尘螨变应原皮肤点刺试验（SPY）以及血清屋尘螨变应原特异性免疫球蛋白E（d1-sIgE）检测。结果3组随着皮肤点刺试验“＋”的递增,屋尘螨变应原结膜激发试验结果＋＋＋以上患者比例逐渐增加,差异无统计学意义（P〉0．05）。结论屋尘螨变应原结膜激发试验不受变应性疾病累及器官的影响,在不伴上气道变态反应性疾病的下气道变态反应性疾病的诊断中亦存在一定的诊断价值。     

深圳地区变应性鼻炎变应原分析

目的了解深圳地区变应性鼻炎的常见变应原。方法对855例疑似变应性鼻炎的患者进行皮肤点刺试验，测定致敏变应原。结果855例疑似变应性鼻炎患者中578例（67．6％）有阳性反应，单一变应原阳性51例，2种以上变应原阳性527例。以吸人性变应原为主，其中65例有哮喘病史。578例阳性病例中屋尘螨阳性率最高，为520例（90％），其次是粉尘螨488例（84．4％）。结论应针对深圳地区变应性鼻炎的常见变应原（屋尘螨、粉尘螨），做好变应原检测工作，提高检测准确率。     

上海局部区域变应性鼻炎变应原流行病学分析

目的了解上海西南片局部区域变应性鼻炎变应原分布情况。方法参照文献方法,应用“阿罗格”变应原皮试液,以组胺为阳性对照,生理盐水为阴性对照,对680例疑似变应性鼻炎患者进行皮肤点刺试验,明确其主要致敏变应原。结果变应原皮试结果显示,436例为阳性（64．12％）,吸入性粉尘螨和屋尘螨的皮试阳性率分别为49．56％和49．26％。结论本试验区域临床变应性鼻炎的主要致敏原为吸入性粉尘螨和屋尘螨。“阿罗格”变应原皮肤点刺试验可明确变应性鼻炎的致敏因素,对该疾病的预防与诊治具有指导意义。     

标准化变应原皮肤点刺试验及免疫治疗在变应性疾病中的临床应用

目的探讨标准化变应原皮肤点刺试验及免疫治疗在变应性疾病中的临床应用。方法对1836例拟诊变态反应性疾病患者用30种阿罗格变应原进行皮肤点刺试验，以生理盐水为阴性对照，组胺为阳性对照。对466例变应性鼻炎患者，应用屋尘螨、粉尘螨及混合螨变应原进行特异性免疫治疗，追踪观察疗效，对相关资料进行统计分析。结果1836例拟诊变应性疾病患者中，1322例阳性（72．0％），其中屋尘螨、粉尘螨的阳性率最高，分别为56．4％和53．2％；标准化变应原免疫治疗持续性变应性鼻炎有效率为86．9％（405／466），无明显不良反应。结论阿罗格变应原皮肤点剌试验安全、敏感、准确，为变应性疾病的诊治提供重要依据；标准化变应原免疫治疗能有效缓解或减轻变应性鼻炎患者的症状，且疗效高、操作简便、不良反应少。     

191例慢性荨麻疹变应原检测分析

目的：了解慢性荨麻疹患者常见变应原的分布情况,为预防和治疗提供参考。方法：采用18种标准化变应原对191例慢性荨麻疹患者进行皮肤点刺试验。结果：变应原皮肤点刺试验总阳性率为75.92％,主要变应原为屋尘螨和粉尘螨,变应原阳性率与性别无关,但与年龄相关,3～39岁者的皮肤点刺试验阳性率高于40～74岁者（ P＜0.05）,吸入性变应原阳性率明显高于食入性变应原（ P＜0.05）。结论：191例慢性荨麻疹患者中,变应原皮肤点刺试验阳性率存在一定的性别、年龄分布特征,吸入性变应原阳性率高于食入性变应原;户尘螨和粉尘螨是其主要致敏原。     

变应性鼻炎吸入性和食入性变应原特异性免疫球蛋白E检测分析

目的 了解广州地区变应性鼻炎（AR）主要吸入性和食入性变应原分布和年龄差异.方法 回顾性分析未成年组（≤18岁）和成年组（〉18岁）AR患者常见吸入性和食入性变应原特异性免疫球蛋白E（IgE）阳性率及其分布差异.结果 吸入性变应原特异性IgE阳性的AR患者638例,其中合并食入性变应原特异性IgE阳性的患者有18.18%（116/638）.吸入性变应原依次为：屋尘螨84.64%、蟑螂18.81%、柏树14.89%、动物毛皮屑组合13.01%、树木花粉组合7.05%、矮豚草5.02%、葎草1.88%、蒿草1.72%、霉菌组合1.41%.未成年组中屋尘螨特异性IgE的阳性率明显高于成年组 （P〈0.05）.116例食入性变应原特异性IgE阳性的患者中未成年组占85.34%（99/116）,成年组占14.66%（17/116）,其中未成年组阳性的比例明显高于成年组（P〈0.05）.食入性变应原依次为：牛奶57.76%、鸡蛋41.38%、牛肉39.66%、羊肉32.76%、虾蟹12.93%、腰果12.07%、小麦11.21%、鱼1.72%、花生黄豆组合1.72%.结论 广州地区AR患者最主要的吸入性变应原依次是屋尘螨、蟑螂、柏树;食入性变应原主要是牛奶、鸡蛋、牛肉;未成年人对食物和螨虫过敏的概率明显高于成年人.     

低pH插入肽-蛋白酶激活受体1复合物抑制三阴性乳腺癌MDA-MB-231细胞增殖的实验研究★

目的 观察低pH插入肽-蛋白酶激活受体1（pHLIP-P1AP）复合物对三阴性乳腺癌（TNBC）MDA-MB-231细胞增殖的影响。方法 设计、合成荧光标记的pHLIP-P1AP。观察MDA-MB-231细胞与MCF-10A细胞表面蛋白酶激活受体1（PAR1）的表达情况。分析不同pH值（7.4、6.0）条件下荧光标记的pHLIP-P1AP与MDA-MB-231细胞的结合情况及其对MDA-MB-231细胞增殖的影响。结果 成功合成了pHLIP-P1AP并进行荧光标记。在酸性环境下（pH 6.0），荧光标记的pHLIP-P1AP与表面高表达PAR1的MDA-MB-231细胞有较强的结合能力，可明显抑制MDA-MB-231细胞的增殖，pHLIP-P1AP为0.5 μg、1 μg、2 μg、4 μg、8 μg时，细胞的增殖抑制率分别为3.39%，5.27%，14.29%，22.14%、35.69%。结论 MDA-MB-231细胞表面表达大量的PAR1。pHLIP-P1AP在酸性环境下能够有效靶向MDA-MB-231细胞，并抑制MDA-MB-231细胞的生长，有望成为治疗TNBC的有价值的新型药物。     

儿童变应性鼻炎吸入性和食入性变应原比较

目的 探讨佛山地区儿童变应性鼻炎（AR）患者吸入性和食入性变应原的种类和分布情况.方法 选取300例近2年门诊儿童AR患者进行吸入性和食入性变应原皮肤点刺试验,分析比较佛山地区AR患者变应原分布特点.结果 300例儿童患者中,吸入组变应原SPT阳性反应243例（81.00％）,变应原排列前位的为屋尘螨、粉尘螨、热带螨、德国小蠊、狗毛;食入组中SPT阳性反应105例（35.00％）,变应原排列依次为螃蟹、虾、花生、桃子.结论 佛山地区AR患者的主要变应原是尘螨、蟑螂及海鲜类食入性变应原.     

Inhibitory effect of retinoic acid on proliferation,maturation and tryptase level in human leukemic mast cells (HMC-1)

Mast cells play important role in allergic inflammation by releasing histamine, tryptase and several inflammatory cytokines. Human leukemic mast cells (HMC-1) have been used to study mast cell mediator and their role in inflammatory mechanisms. HMC-1 contain and release several inflammatory mediators, of which the proteolytic enzyme tryptase is most characteristic. Retinoids, including retinoic acid, are naturally occurring and synthetic derivatives of vitamin A. All-trans-retinoic (ATRA) acid had been previously reported to inhibit cell proliferation, differentiation and apoptosis. In the present study, we investigated the effect of ATRA on the proliferation and secretion of tryptase in HMC-1. HMC-1 were treated with ATRA at 10(-4M), 10(-5M) or 10(-6M) for 3, 4 or 5 days in culture. Control HMC-1 were treated with equal amount of culture medium only. ATRA decreased the number of HMC-1 as compared to the control group. The same treatment for 3, 4 or 5 days also decreased intracellular tryptase levels. These results indicate that ATRA significantly inhibits both proliferation and growth as shown by the decreased intracellular tryptase levels in HMC-1. ATRA may be a useful agent in the treatment of mast cell proliferative disorders.     

Activation of human tonsil and skin mast cells by agonists of proteinase activated receptor-2

Aim: To investigate the effects of the agonists of proteinase activated receptor (PAR)-2,and histamine on degranulation of human mast cells. Methods: Human mast cells were enzymatically dispersed from tonsil and skin tissues. The dispersed cells were then cultured with various stimuli, and tryptase and histamine levels in cell supernatants collected from challenge tubes were measured. Results:PAR-2 agonist peptide SLIGKV provoked a dose-dependent release of histamine from skin mast cells. It also induced tryptase release from tonsil mast cells, tcLIGRLO appeared less potent than SLIGKV in induction of release of histamine and tryptase. Trypsin was able to induce a “bell” shape increase in tryptase release from tonsil mast cells. It was also able to induce a dose-dependent release of histamine from both tonsil and skin mast cells. The actions of trypsin on mast cells were inhibited by soy bean trypsin inhibitor (SBTI) or α1-antitrypsin (α1-AT).Time course study revealed that both stimulated tryptase or histamine release initiated within 10s and reached their peak release between 4 and 6min. Pretreatment of cells with metabolic inhibitors or pertussis toxin reduced the ability of mast cells to release tryptase or histamine. Conclusion: It was demonstrated that the in vitro tryptase release properties of human tonsil and skin mast cells suggested a novel type of mast cell heterogeneity. The activation of mast cells by PAR-2 agonists indicated a self-amplification mechanism of mast cell degranulation.     

Glycosylation and the activation of proteinase-activated receptor 2 (PAR(2)) by human mast cell tryptase

1. Human mast cell tryptase appears to display considerable variation in activating proteinase-activated receptor 2 (PAR(2)). We found tryptase to be an inefficient activator of wild-type rat-PAR(2) (wt-rPAR(2)) and therefore decided to explore the factors that may influence tryptase activation of PAR(2). 2. Using a 20 mer peptide (P20) corresponding to the cleavage/activation sequence of wt-rPAR(2), tryptase was as efficient as trypsin in releasing the receptor-activating sequence (SLIGRL.). However, in the presence of either human-PAR(2) or wt-r PAR(2) expressing cells, tryptase could only activate PAR(2) by releasing SLIGRL from the P20 peptide, suggesting that PAR(2) expressed on the cells was protected from tryptase activation. 3. Three approaches were employed to test the hypothesis that PAR(2) receptor glycosylation restricts tryptase activation. (a) pretreatment of wt-rPAR(2) expressing cells or human embryonic kidney cells (HEK293) with vibrio cholerae neuraminidase to remove oligosaccharide sialic acid, unmasked tryptase-mediated PAR(2) activation. (b) Inhibiting receptor glycosylation in HEK293 cells with tunicamycin enabled tryptase-mediated PAR(2) activation. (c) Wt-rPAR(2) devoid of the N-terminal glycosylation sequon (PAR(2)T25(-)), but not rPAR(2) devoid of the glycosylation sequon located on extracellular loop-2 (PAR(2)T224A), was selectively and substantially (>30 fold) more sensitive to tryptase compared with the wt-rPAR(2). 4. Immunocytochemistry using antisera that specifically recognized the N-terminal precleavage sequence of PAR(2) demonstrated that tryptase released the precleavage domain from PAR(2)T25(-) but not from wt-rPAR(2). 5. Heparin : tryptase molar ratios of greater than 2 : 1 abrogated tryptase activation of PAR(2)T25(-). 6. Our results indicate that glycosylation of PAR(2) and heparin-inhibition of PAR(2) activation by tryptase could provide novel mechanisms for regulating receptor activation by tryptase and possibly other proteases.     

Characterization of protease-activated receptors in rat peritoneal mast cells

Activation of protease-activated receptor (PAR)-1 or PAR-2 elicits inflammation most probably via mast cell degranulation in vivo. The present study aimed at characterizing PARs in rat peritoneal mast cells (PMC). Messenger RNA for PAR-1, but not for PAR-2, was detected in PMC. Thrombin, the PAR-1 agonist SFLLR-NH2 or the PAR-2 agonist SLIGRL-NH2 failed to induce histamine release from PMC. Surprisingly, the PAR-2-inactive control peptide LSIGRL-NH2 triggered histamine release from PMC. Thus, PAR-1, but not PAR-2, are expressed in PMC, whereas neither PAR-1 nor PAR-2 are considered to be involved in degranulation of PMC. LSIGRL-NH2 does not appear to be appropriate as a control peptide for PAR-2 in inflammation studies.     

Inhibition of dipeptidyl peptidase I in the human mast cell line HMC-1: blocked activation of tryptase, but not of the predominant chymotryptic activity

The mast cell proteases tryptase and chymase are synthesised as inactive precursors, but are stored and secreted as active enzymes. The cysteinyl protease dipeptidyl peptidase I (DPPI, cathepsin C) can activate the corresponding proenzymes in cell-free systems, but it is unknown whether it fulfils this role within the intact cell. We, therefore, tested the effect the DPPI-selective inhibitor Gly-Phe diazomethyl ketone (Gly-Phe-CHN(2)) on the tryptic and chymotryptic activity of the human mast cell-like cell line, HMC-1, and monitored any changes in the amount of immunodetectable enzymes by flow cytometry. Culture in Gly-Phe-CHN(2) produced a significant decrease in tryptase activity in cell lysates within 24hr and further decreases during continued culturing to 216 hr with periodic replenishment of Gly-Phe-CHN(2)-containing media. Flow cytometry showed no significant change in the levels of immunoreactive tryptase. In contrast, chymotryptic activity in treated cells did not differ significantly from untreated cells at any time point. Treatment of 216 hr cell lysates with DPPI revealed significant amounts of activatable protryptase in Gly-Phe-CHN(2)-treated cells, but not in controls, whereas activatable prochymotryptic activity was found in both treated and control cells. Chymase was detected immunologically, though small differences in substrate specificity and molecular mass were observed. These results strongly suggest that DPPI plays a role in the activation of tryptase, but not of the predominant chymotryptic activity of HMC-1 cells. As inhibitors of tryptase have proven efficacious in models of allergic disease, these results also indicate that inhibitors of DPPI might provide an additional point of therapeutic control.     

The role of protease-activated receptor-2 (PAR2) in the modulation of beating of the mouse isolated ureter: lack of involvement of mast cells or sensory nerves

1 The localization of protease-activated receptor-2 (PAR2) and the effects of PAR2 activators were investigated in the mouse isolated ureter in order to test the hypothesis that PAR2 activation may initiate neuropeptide release from sensory nerve fibres and hence contribute to inflammation. 2 PAR2 was localized by fluorescence immunohistochemistry to both the smooth muscle and epithelium of the ureter. Macrophage-like cells in the adventitia of the ureter were also PAR2-immunoreactive. PAR2-immunoreactivity was not observed in mast cells or nerve fibres. 3 In circular muscle preparations of the ureter in which continuous rhythmic beating was induced by KCl (20 mM) and the thromboxane A2 mimetic U46619 (0.3 microM), trypsin (0.3 U ml-1) reduced beat frequency to 84.6+/-2.0% of control rates. The PAR2-selective peptide agonist SLIGRL-NH2 concentration-dependently (0.1-3.0 microM) slowed beat frequency to a maximum of 72.7+/-2.0%. 4 Histamine (1-300 microM) was more efficacious than SLIGRL-NH2 in inhibiting ureter beat frequency in a concentration-dependent manner to a maximum (at 300 microM) of 7.9+/-2.5% of the control rate. 5 Pretreatment of preparations with capsaicin (10 microM for 30 min) markedly attenuated the inhibitory effect of histamine, but not that of SLIGRL-NH2, indicating a role for sensory nerves in the inhibitory effect of histamine only. 6 The inhibitory effect of SLIGRL-NH2 on ureter beat frequency was unaffected by the nitric oxide (NO) synthase inhibitor, L-NOARG (100 microM) or the cyclo-oxygenase inhibitor, indomethacin (3 microM). 7 In conclusion, PAR2 activation causes inhibition of beating in the mouse ureter that is not mediated by axon reflex release of inhibitory neuropeptides. This inhibitory effect of PAR2 appears to be mediated directly on smooth muscle cells, although the contribution of non-NO, non-prostanoid epithelium-derived factors cannot be ruled out.     

Differential DNA synthesis in response to activation of protease-activated receptors on cultured guinea-pig tracheal smooth muscle cells

Both thrombin and tryptase have been shown to induce smooth muscle cell proliferation in vitro. We have used cultured primary guinea-pig tracheal smooth muscle in order to define pharmacologically the receptors involved in this effect. Tryptase, a protease-activated receptor (PAR)-2 agonist, induced DNA synthesis up to the second passage of the cells, thereafter the response waned. In contrast, thrombin, a PAR-1 agonist, and the PAR-1 activating peptide (SFLLRN) induced DNA synthesis starting from the third passage only. Thrombin and tryptase responses were dose-dependently inhibited by leupeptin. The selective PAR-2 activating peptide (SLIGRL-NH(2)) was unable to induce DNA synthesis in cells from passages 1 to 6. In agreement with the functional data, mRNA expression for PAR-1 was increased in cells in later passages. In contradiction with the functional data, however, equal mRNA expression for PAR-2 was found in all passages. These results suggest that thrombin induces guinea-pig tracheal smooth muscle DNA synthesis through activation of PAR-1. However, the differential effect of tryptase and SLIGRL-NH(2) suggests that tryptase might exert some of its effect via a non-PAR-2 receptor.     

High glucose increases the expression of proinflammatory cytokines and secretion of TNFα and β-hexosaminidase in human mast cells

Epidemiological studies demonstrated that obesity, which is a high-risk factor for development of hyperglycemia-associated metabolic syndromes, is associated with prevalence/incidence of allergic diseases. To elucidate the underlying mechanisms of the relationship between hyperglycemia and allergy, we examined the effect of high glucose on the activation of human mast cell lines, HMC-1 and LAD2. HMC-1 and LAD2 cells were cultured in low (5.5 mM) and high (25 mM)-glucose Dulbecco's modified Eagle's medium (DMEM). High-glucose medium increased the intracellular reactive oxygen species levels in HMC-1 and LAD2 cells after 2 days of incubation; in HMC-1 cells, the expression levels of tumor necrosis factor (TNF) α, interleukin (IL)-1β, IL-6, and IL-13 were increased significantly. The β-hexosaminidase release rates were not significantly different between LAD2 cells cultured in both media; however, the intracellular and extracellular activities of β-hexosaminidase in cells were significantly higher in high-glucose than in low-glucose media. High glucose increased the secretion of TNFα by unstimulated HMC-1 cells and IgE crosslinking-stimulated LAD2 cells. High glucose increased the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinases (MAPKs), which regulate the expression of TNFα and other inflammatory cytokines, in both HMC-1 and LAD2 cells. Thus, high glucose increased the expression of proinflammatory and proallergic cytokines, the secretion of TNFα, and β-hexosaminidase activity in human mast cells. Our result suggests that hyperglycemia promotes the activation of human mast cells associated with allergy and inflammation under unstimulated and stimulated conditions.     

Review article: proteinase-activated receptors - novel signals for gastrointestinal pathophysiology

Proteinase-activated receptors (PARs) have the common property of being activated by the proteolytic cleavage of their extracellular N-terminal domain. The new NH2-terminus acts as a 'tethered ligand' binding and activating the receptor itself. Four members of this family have been cloned, three of which are activated by thrombin (PAR-1, PAR-3 and PAR-4) while the fourth (PAR-2) is activated by trypsin or mast cell tryptase. In physiological or pathophysiological conditions, the gastrointestinal tract is exposed more than other tissues to proteinases (digestive enzymes, proteinases from pathogens or proteinases from inflammatory cells) that can activate PARs. Since PARs are highly expressed throughout the gastrointestinal tract, the study of the role of PARs in these tissues appears to be particularly important. It has already been shown that PAR-2 activation induces calcium mobilization and eicosanoid production in enterocytes as well as changes in ion transport in jejunal tissue segments. PAR-2 activation also causes calcium mobilization and stimulates amylase release from pancreatic acini. Moreover, both PAR-1 and PAR-2 activation can alter the gastrointestinal motility. In inflammatory or allergic conditions, the proteinases that constitute the major agonists for PARs (thrombin, trypsin and mast cell tryptase) are usually released. The activation of PARs by these proteinases might contribute to the gastrointestinal disorders associated with these pathologies. A complete understanding of the role of PARs in the gastrointestinal tract will require the development of selective receptor antagonists that are not yet available. Nonetheless, the use of PAR agonists has already highlighted new potential functions for proteinases in the gastrointestinal tract, thus the control of PAR activation might represent a promising therapeutic target.     

Molecular mechanisms of anti-inflammatory effect of chrysophanol,an active component of AST2017-01 on atopic dermatitis in vitro models

AST2017-01 mainly consists of Rumex crispus and -Cordyceps militaris and has been widely consumed as an herbal medicine or functional food in Korea. Here we investigated the influences of AST2017-01 and its active component, chrysophanol on human mast cell (HMC-1 cell) and human keratinocyte (HaCaT cell)-mediated inflammatory reactions. Pretreatment with AST2017-01 or chrysophanol suppressed intracellular calcium levels and histamine release in phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-treated HMC-1 cells. Levels of phosphorylated-mitogen-activated protein kinase increased by PMACI stimulation were reduced by AST2017-01 or chrysophanol pretreatment. Protein levels of IκB kinaseβ and receptor-interacting protein 2 in PMACI-treated HMC-1 cells were decreased by AST2017-01 or chrysophanol pretreatment. Pretreatment with AST2017-01 or chrysophanol significantly blocked PMACI-induced activation of caspase-1 and nuclear factor-κB. In addition, pretreatment with AST2017-01 or chrysophanol significantly decreased the PMACI-induced levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and thymic stromal lymphopoietin (TSLP) on HMC-1 cells. In activated HaCaT cells, pretreatment with AST2017-01 or chrysophanol significantly reduced production of TSLP and activation of caspase-1. In conclusion, these findings indicate that chrysophanol is an active component of AST2017-01 and AST2017-01 acts as a novel potent anti-inflammatory herbal medicine or functional food.