ArticleCell death & disease2016
The anti-apoptotic Bcl-2 family protein A1/Bfl-1 regulates neutrophil survival and homeostasis and is controlled via PI3K and JAK/STAT signaling.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 92 citations in OpenAlex.
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- Anti-apoptotic BCL-2 family proteins: from regulatory networks to therapeutic targeting.Oncogenesis · 2026Review
- Methyltransferase SETD7 as a Regulator of STING-Dependent Cytokine Response in Lung Cancer Cells.International journal of molecular sciences · 2026Article
- CAR-engineered cell therapies: current understandings and future perspectives.Molecular biomedicine · 2026Review
- Tracking NF-kB activity across steady-state neutrophil maturation.Cell death discovery · 2025Article
- Role of Neutrophils in Homeostasis and Diseases.MedComm · 2025Review
- Cysteine‑ and glycine‑rich protein 2: A vital regulator that inhibits necroptosis glioma cell by activating the JAK‑STAT1 pathways.Oncology reports · 2025Article
- Hybridization-based discovery of novel quinazoline-2-indolinone derivatives as potent and selective PI3Kα inhibitors.Journal of advanced research · 2025Article
- New insights into constitutive neutrophil death.Cell death discovery · 2025Review
- Article
- Machine learning integration identifying an eight-gene diagnostic signature for acute mountain sickness.Frontiers in medicine · 2025Article
- The Intensity of BCL2A1 Expression Increases According to the Stage Progression of Acute Histologic Chorioamnionitis in the Extra-Placental Membranes of Spontaneous Preterm Birth.Life (Basel, Switzerland) · 2024Article
- Contribution of A1 to macrophage survival in cooperation with MCL-1 and BCL-XCell death & disease · 2024Article
- Identification of hub genes associated with neutrophils in chronic rhinosinusitis with nasal polyps.Scientific reports · 2024Article
- Disrupting Smad3 potentiates immunostimulatory function of NK cells against lung carcinoma by promoting GM-CSF production.Cellular and molecular life sciences : CMLS · 2024Article
- Decoding the intricacies: a comprehensive analysis of microRNAs in the pathogenesis, diagnosis, prognosis and therapeutic strategies for COVID-19.Frontiers in medicine · 2024Review
- Key pathways and genes that are altered during treatment with hyperbaric oxygen in patients with sepsis due to necrotizing soft tissue infection (HBOmic study).European journal of medical research · 2023Observational
- A1 is induced by pathogen ligands to limit myeloid cell death and NLRP3 inflammasome activation.EMBO reports · 2023Article
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutrophil granulocytes are innate effector cells of the first line of defense against pyogenic bacteria. Neutrophil lifespan is short, is prolonged by pro-inflammatory stimuli, controls functionality of the cells and can determine tissue damage. Experimental analysis of primary neutrophils is difficult because of their short lifespan and lack of possibilities of genetic manipulation. The Hoxb8 system of neutrophil differentiation from immortalized progenitor cells offers the advantage of unlimited production of neutrophils in vitro as well as easy genetic modification. We here use this system to analyze the role of the poorly characterized anti-apoptotic B-cell lymphoma protein 2 (Bcl-2) family member A1/Bfl-1 (Bcl-2-related protein A1) for survival and homeostasis of neutrophils and of neutrophil progenitors. Low constitutive mRNA and protein expression of A1 was detected, while A1 was transiently upregulated early during differentiation. Pro-inflammatory stimuli caused strong, mainly transcriptional, A1 upregulation, in contrast to posttranscriptional regulation of Mcl-1 (induced myeloid leukemia cell differentiation protein). Inhibitor studies showed that phosphoinositide-3 kinase (PI3K)/Akt and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) is required for A1 expression and survival of progenitors and mature neutrophils. ShRNA-mediated constitutive A1 knockdown (KD) impaired maintenance of progenitors. ShRNA experiments further showed that A1 was required early during neutrophil differentiation as well as in mature neutrophils upon pro-inflammatory stimulation. Our data further indicate differential regulation of the two anti-apoptotic proteins A1 and Mcl-1. Relevant findings were confirmed in primary human neutrophils. Our data indicate that A1, in addition to the well-established Mcl-1, substantially contributes to neutrophil survival and homeostasis. A1 may thus be a promising target for anti-inflammatory therapy.
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