CREB transcription factor modulates Bcl2 transcription in response to C5a in HL-60-derived neutrophils

European Journal of Clinical Investigation
M C PerianayagamB L Jaber

Abstract

Complement fragment C5a and neutrophils have been implicated in the pathogenesis of renal disease and C5a has also been shown to delay apoptosis of human neutrophils via a transcription-independent pathway. However, transcription-dependent pathways have not been well described. The present study examined whether activation of HL-60-derived neutrophils by C5a modulates the transcription of two members of the Bcl2 family, Bax (pro-apoptotic) and Bcl2 (anti-apoptotic) molecules, and whether the cAMP-response element-binding protein (CREB) transcription factor mediates these effects through the phosphatidylinositol 3-kinase (PI3K)/Akt and extra-cellular signal-regulated kinase (ERK) signalling pathways. The human promyelocytic leukaemia HL-60 cell line was differentiated into neutrophils using 1.25% DMSO. Differentiated cells were incubated with recombinant human C5a for 30-120 min with, or without, pretreatment with wortmannin or PD98059. The cells were lysed and quantified for gene-specific Bax and Bcl2 mRNA. In separate experiments, cells were incubated with C5a for 5-30 min with, or without, pretreatment with wortmannin, PD98059, or alkaline phosphatase. Cells were then lysed and immunoblotted using antihuman phospho-CREB (Ser1...Continue Reading

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Citations

Dec 30, 2006·Apoptosis : an International Journal on Programmed Cell Death·David H W ChauDecheng Yang
Jul 3, 2007·British Journal of Pharmacology·P N MonkD P Fairlie
Nov 15, 2012·Journal of Cellular Biochemistry·Seon Sook KimSu Ryeon Seo
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Aug 1, 2014·Nature·Diogo Fonseca-PereiraHenrique Veiga-Fernandes
Feb 5, 2015·Molecular and Cellular Biochemistry·Jin QianYong-Ping You
Jun 25, 2019·Frontiers in Immunology·Anna LenkiewiczMariusz Z Ratajczak
Jul 25, 2021·Journal of Clinical Medicine·Christian EhrnthallerMarkus Huber-Lang

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