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

Cellular & Molecular Immunology volume 11, pages 105–106 (2014)Cite this article

Abstract

Tumor-necrosis factor-α (TNF-α)-driven nuclear factor-κB (NF-κB) activation and apoptosis are opposing pathways; the growing recognition of these conflicting roles of TNF-α is perplexing. Here, we show that inflammation and apoptosis are time-phased events following TNF-α signaling and that emergence of suppressor of cytokine signaling 3 (SOCS3) expression limits the ongoing NF-κB activation and promotes apoptosis; further, we suggest an altered view of how inflammatory diseases are initiated and sustained. In vitro, TNF-α (50 ng/ml) induced granulocyte SOCS3 protein, inhibited nuclear accumulation of the p65NF-κB 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-κB 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-α signaling. As apoptosis is associated with SOCS3 abundance, we suggest that these divergent TNF-α-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 therapy.

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Acknowledgements

This is CSIR-IITR communication # 3009. JKC is a recipient of a University Grant Commissions-Senior Research Fellowship. This work was supported by CSIR, New Delhi (NWP-33). JKC was involved in the experimentation and the acquisition, analysis, and interpretation of data and searched the literature and helped in the critical revision of the manuscript for important intellectual contents; BC helped in the revision of the manuscript for intellectual contents; BNP obtained funding and was involved in conceptualizing and designing the study, interpreting the data, drafting the manuscript and supervising the study overall.

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  1. Immunobiology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India

    Jasmeet Kaur Chhabra & Bhola Nath Paul

  2. Department of Physics, Faculty of Science, Jadavpur University, Kolkata, India

    Brajadulal Chattopadhyay

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Chhabra, J., Chattopadhyay, B. & Paul, B. SOCS3 dictates the transition of divergent time-phased events in granulocyte TNF-α signaling. Cell Mol Immunol 11, 105–106 (2014). https://doi.org/10.1038/cmi.2013.36

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