Differential changes in gene expression in human neutrophils following TNF-α stimulation: Up-regulation of anti-apoptotic proteins and down-regulation of proteins involved in death receptor signaling.



Chiewchengchol, Direkrit, Wright, Helen L ORCID: 0000-0003-0442-3134, Thomas, Huw B, Lam, Connie W, Roberts, Kate J, Hirankarn, Nattiya, Beresford, Michael W ORCID: 0000-0002-5400-9911, Moots, Robert J ORCID: 0000-0001-7019-6211 and Edwards, Steven W ORCID: 0000-0002-7074-0552
(2016) Differential changes in gene expression in human neutrophils following TNF-α stimulation: Up-regulation of anti-apoptotic proteins and down-regulation of proteins involved in death receptor signaling. Immunity, inflammation and disease, 4 (1). 35 - 44.

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Abstract

Responses of human neutrophils to TNF-α are complex and multifactorial. Exposure of human neutrophils to TNF-α in vitro primes the respiratory burst, delays apoptosis and induces the expression of several genes including chemokines, and TNF-α itself. This study aimed to determine the impact of TNF-α exposure on the expression of neutrophil genes and proteins that regulate apoptosis. Quantitative PCR and RNA-Seq, identified changes in expression of several apoptosis regulating genes in response to TNF-α exposure. Up-regulated genes included TNF-α itself, and several anti-apoptotic genes, including BCL2A1, CFLAR (cFLIP) and TNFAIP3, whose mRNA levels increased above control values by between 4-20 fold (n = 3, P < 0.05). In contrast, the expression of pro-apoptotic genes, including CASP8, FADD and TNFRSF1A and TNFRSF1B, were significantly down-regulated following TNF-α treatment. These changes in mRNA levels were paralleled by decreases in protein levels of caspases 8 and 10, TRADD, FADD, TNFRSF1A and TNFRSF1B, and increased cFLIP protein levels, as detected by western blotting. These data indicate that when neutrophils are triggered by TNF-α exposure, they undergo molecular changes in transcriptional expression to up-regulate expression of specific anti-apoptotic proteins and concomitantly decrease expression of specific proteins involved in death receptor signaling which will alter their function in TNF-α rich environments.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 07 Dec 2015 10:02
Last Modified: 03 Jan 2020 14:10
DOI: 10.1002/iid3.90
URI: http://livrepository.liverpool.ac.uk/id/eprint/2041259