SOCS3 dictates the transition of divergent time-phased events in granulocyte TNF-a signaling

作     者：Jasmeet Kaur Chhabra Brajadulal Chattopadhyay Bhola Nath Paul 

作者机构：Immunobiology Division CSlR-Indian Institute of Toxicology Research Lucknow India Department of Physics Faculty of Science JadavpurUniversity Kolkata India 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2014年第11卷第1期

页      面：105-116页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

基　　金：supported by CSIR  New Delhi 

主　　题：apoptosis granulocytes lung inflammation NF-kB TNF-a SOCS3 

摘      要：Tumor-necrosis factor-a （TNF-a）-driven nuclear factor-KB （NF-KB） activation and apoptosis are opposing pathways; the growing recognition of these conflicting roles of TNF-a is perplexing. Here, we show that inflammation and apoptosis are time-phased events following TNF-a signaling and that emergence of suppressor of cytokine signaling 3 （SOCS3） expression limits the ongoing NF-KB activation and promotes apoptosis; further, we suggest an altered view of how inflammatory diseases are initiated and sustained. In vitro, TNF-a （50 ng/ml） induced granulocyte SOCS3 protein, inhibited nuclear accumulation of the p65NF-KB subunit and enhanced apoptosis, as shown by DNA laddering, annexin V positivity, and overexpression of caspase-3 and Bax in the late phase, whereas the early phase was marked by NF-KB activation. Conversely, SOCS3 knockdown by small interfering RNA （siRNA） inhibited granulocyte apoptosis and enhanced nuclear accumulation of p65 and 5＇ lipooxygenase expression in the late phase of TNF-a signaling. As apoptosis is associated with SOCS3 abundance, we suggest that these divergent TNF-a-driven events are time-phased, interconnected, opposing control mechanisms and one of the central features through which the immune system resolves pulmonary inflammation. Dysregulation may initiate mucosal inflammation, thus changing the landscape of asthma theraov.