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TNF-α and Poly(I:C) induction of A20 and activation of NF-κB signaling are independent of ABCF1 in human airway epithelial cells.
Scientific Reports 2023 September 8
ABCF1 is the most characterized member of the ABCF family in eukaryotes with proposed functions related to innate immunity in fibroblasts, macrophages, and epithelial cells. Currently, a mechanistic link between ABCF1 and immune responses in human airway epithelial cells (HAECs) remains to be clearly defined. The present study aimed at characterizing the function of ABCF1 in the context of nuclear factor nuclear factor κB (NF-κB) mediated pro-inflammatory responses in an immortalized human airway epithelial cell line, HBEC-6KT. We demonstrated that with ABCF1 silencing under basal conditions, TNF Alpha Induced Protein 3 (TNFAIP3/A20) protein expression and downstream expression and activation of transcription factors, NF-κB and Interferon regulatory factor 3 (IRF-3), were not disrupted. We followed with investigations of ABCF1 function under a pro-inflammatory stimuli that are known to be regulated by A20. We demonstrated that under Polyinosinic:polycytidylic acid (Poly(I:C)) and tumor Necrosis Factor-α (TNF-α) challenge with ABCF1 silencing, there was a significant reduction in secreted levels of interleukin-8 (IL-8) and a trend for reduced IL-6. However, we observed no changes to the expression levels of A20 and the activation status of the transcription factors, NF-κB and IRF-3. Collectively, these studies demonstrate that Poly(I:C) and TNF-α induced IL-8 is regulated by ABCF1 via pathways independent of NF-κB and IRF-3 activation.
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