Kim Mi-Sun, You Hyun Ja, You Mi Kyung, Kim Nam-Song, Shim Bum Sang, Kim Hyung-Min
College of Oriental Medicine, Kyung Hee University, Seoul, South Korea.
Immunopharmacol Immunotoxicol. 2004 Aug;26(3):401-9. doi: 10.1081/iph-200026887.
Mast cells are known to play an active role as effector cells in allergic inflammation and in diverse immunological and pathological processes. Activated mast cell-derived pro-inflammatory cytokines are important pathologic factors of progression of allergic inflammation. In this study, we investigated whether pro-inflammatory cytokines (TNF-alpha and IL-8) can be induced by calcium stimulation in HMC-1 cells, and high molecular weight water-soluble chitosan (WSC) can inhibit the production of these cytokines. We provided evidence that the secretion of TNF-alpha and IL-8 from HMC-1 cells was induced by Ca2+-ionophore A23187 or Ca2+-ATPase inhibitor TSG. Treatment of WSC (10 microg/ml) prior to stimulation with calcium agonists significantly blocked the secretion of TNF-alpha by 65.1% for A23187 and 87.7% for TSG. IL-8 secretion in response to A23187 or TSG was inhibited by 49.2% for A23187 and 34.1% for TSG, respectively, compared to absence of WSC. These results suggest that WSC has potential regulatory effects on allergic inflammatory diseases by down-modulating Ca2+-induced mast cell activation.
已知肥大细胞在过敏性炎症以及多种免疫和病理过程中作为效应细胞发挥积极作用。活化的肥大细胞衍生的促炎细胞因子是过敏性炎症进展的重要病理因素。在本研究中,我们调查了促炎细胞因子(肿瘤坏死因子-α和白细胞介素-8)是否可由钙刺激在HMC-1细胞中诱导产生,以及高分子量水溶性壳聚糖(WSC)是否能抑制这些细胞因子的产生。我们提供的证据表明,HMC-1细胞中肿瘤坏死因子-α和白细胞介素-8的分泌是由钙离子载体A23187或钙ATP酶抑制剂TSG诱导的。在用钙激动剂刺激之前用WSC(10微克/毫升)处理,可显著阻断肿瘤坏死因子-α的分泌,对于A23187为65.1%,对于TSG为87.7%。与不存在WSC相比,对A23187或TSG应答的白细胞介素-8分泌分别被抑制了49.2%(对于A23187)和34.1%(对于TSG)。这些结果表明,WSC通过下调钙诱导的肥大细胞活化对过敏性炎症疾病具有潜在的调节作用。