Role of TNF-α and extracellular ATP in THP-1 cell activation following allergen exposure
Role of TNF-α and extracellular ATP in THP-1 cell activation following allergen exposure
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TNF-α 和细胞外 ATP 在过敏原暴露后 THP-1 细胞激活中的作用
DOI：
10.2131/jts.33.71
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发表时间：
2008
影响因子：
2
通讯作者：
N. Nishiyama
中科院分区：
文献类型：
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作者：
M. Miyazawa;Yuichi Ito;Nanae Kosaka;Y. Nukada;H. Sakaguchi;Hiroyuki Suzuki;N. Nishiyama
树突状细胞（DC），包括朗格汉斯细胞（LC），在过敏性接触性超敏反应的诱导阶段起着关键作用。在暴露于皮肤中的化学过敏原之后，LC经历成熟过程，导致共刺激分子（诸如⑶ 86、⑶ 54和⑶ 40）的表达上调。我们以前的研究表明，化学过敏原诱导表型改变（例如，CD 86、CD 54和CD 40）和细胞因子（TNF-α和IL-8）的产生，这可能反映了皮肤致敏过程中树突状细胞的成熟。然而，化学过敏原表型改变的生理信号仍然没有完全理解。因此，在本研究中，我们研究了TNF-α和细胞外ATP对化学变应原诱导的THP-1细胞活化的影响。动力学研究表明，TNF-α和IL-8的释放以时间依赖性方式发生，两种细胞因子在暴露于众所周知的半抗原DNCB和NiSO 4后3小时开始释放。重组人TNF-α以剂量依赖性方式增加CD 54和CD 40表达，而rhTNF-α不增加CD 86表达。此外，中和TNF-α活性强烈抑制过敏原诱导的CD 54和CD 40表达。相反，细胞外ATP诱导的上调CD 86和CD 54的表达。在P2受体拮抗剂苏拉明的存在下，由过敏原引起的CD 86和CD 54表达的上调被部分抑制。因此，我们推测，不仅TNF-α，而且细胞外ATP可能有助于过敏原刺激后的细胞活化，这可能反映了DCs对过敏原的反应机制。
Dendritic cells (DCs), including Langerhans cells (LCs), play a critical role in the induction phase of allergic contact hypersensitivity. Following exposure to chemical allergens in the skin, LCs undergo a maturation process leading to the up-regulation of expression of co-stimulatory molecules, such as CD86, CD54 and CD40. Our previous study revealed that chemical allergens induce phenotype alterations (e.g., CD86, CD54 and CD40) and cytokine production (TNF-α and IL-8) in THP-1 cells that possibly reflect the maturation of dendritic cells during skin sensitization. However, the physiological signals for phenotypic alterations by chemical allergens are still not fully understood. Therefore, in this study, we investigated the effect of TNF-α and extracellular ATP on THP-1 cell activation induced by chemical allergens. Kinetic studies revealed that TNF-α and IL-8 release occurred in a time-dependent manner with release of two cytokines beginning at 3 hr post-exposure to well-known haptens, DNCB and NiSO4. While recombinant human TNF-α augmented CD54 and CD40 expression in a dose-dependent manner, rhTNF-α did not increase CD86 expression. Furthermore, neutralization of TNF-α activity strongly inhibited CD54 and CD40 expression induced by allergens. On the contrary, extracellular ATP induced the up-regulation of both CD86 and CD54 expression. In the presence of the P2 receptor antagonist suramin, the up-regulation of CD86 and CD54 expression by allergens was in part suppressed. Therefore, we postulate that not only TNF-α but also extracellular ATP may contribute to cell activation following allergen stimulation, which might reflect the mechanism by which DCs respond to allergens.
DOI：
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发表时间：
2005
期刊：
--
影响因子：
--
作者：
Bertil;-B.;Fredholm;Maria;-P.;Abbracchio;Geoffrey;Burnstock;John;-W.;Daly;-T.;Kendall
通讯作者：
Bertil;-B.;Fredholm;Maria;-P.;Abbracchio;Geoffrey;Burnstock;John;-W.;Daly;-T.;Kendall