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

Authors
  • Chhabra, Jasmeet Kaur
  • Chattopadhyay, Brajadulal
  • Paul, Bhola Nath
Type
Published Article
Journal
Cellular and Molecular Immunology
Publisher
Springer Nature
Publication Date
Jan 01, 2014
Volume
11
Issue
1
Pages
105–106
Identifiers
DOI: 10.1038/cmi.2013.36
PMID: 24037182
Source
Medline
License
Unknown

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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