Gong Jian, Chen Swey-Shen
Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, CA, USA.
Int Immunopharmacol. 2003 Dec;3(13-14):1841-52. doi: 10.1016/j.intimp.2003.08.010.
Antigen-presenting cells (APC) provide two essential signals, e.g., antigenic peptides as well as costimulatory molecules for T-cell activation. Small molecules of smoke tobacco extracts (SM-STE) inhibited antigen presentation of A20 to OVAp-specific T-cell hybridomas. Pretreatment of A20 but not T hybridomas abrogates the APC function. Viability of APC and levels of MHCII, CD40 and B7 of APC were not affected by this treatment. The active principle, inhibiting APC was reproduced with pure tobacco polyphenols, quercetin and its glycoside, rutin. Antioxidant activity of rutin is relevant since rutin downregulated levels of reactive oxygen species (ROS) in phorbol ester-stimulated A20; moreover, another antioxidant, N-acetyl cysteine (NAC) also inhibited antigen presentation, albeit at a higher concentration. Other types of APC, such as bone marrow-derived mast cells (BMMC), MHCII-transfected fibroblast, and splenocytes are affected by tobacco polyphenols. We propose that polyphenols may affect redox-sensitive signal transduction pathway since APC function of PD 98059, MEK inhibitor-pretreated A20 were similarly abrogated. Taken together, we propose that maintaining appropriate intracellular redox of APC is crucial for its antigen-presenting function.
抗原呈递细胞（APC）为T细胞活化提供两种重要信号，即抗原肽和共刺激分子。烟草提取物小分子（SM-STE）抑制A20向OVAp特异性T细胞杂交瘤的抗原呈递。对A20而非T杂交瘤进行预处理可消除APC功能。这种处理不影响APC的活力以及APC的MHCII、CD40和B7水平。抑制APC的活性成分可由纯烟草多酚、槲皮素及其糖苷芦丁重现。芦丁的抗氧化活性具有相关性，因为芦丁可下调佛波酯刺激的A20中活性氧（ROS）水平；此外，另一种抗氧化剂N-乙酰半胱氨酸（NAC）也能抑制抗原呈递，尽管所需浓度更高。其他类型的APC，如骨髓来源的肥大细胞（BMMC）、MHCII转染的成纤维细胞和脾细胞也受烟草多酚影响。我们提出多酚可能影响氧化还原敏感的信号转导途径，因为用MEK抑制剂PD 98059预处理的A20的APC功能同样被消除。综上所述，我们认为维持APC适当的细胞内氧化还原状态对其抗原呈递功能至关重要。
