ArticleThe Journal of experimental medicine1999
FLICE-inhibitory protein expression during macrophage differentiation confers resistance to fas-mediated apoptosis.
Article in The Journal of experimental medicine, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 221 citations in OpenAlex.
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- Review
- Fas Ligand enhances vessel maturation and inhibits vascular leakage associated with age-related macular degeneration.Research square · 2024Article
- Apoptosis Regulation in Osteoarthritis and the Influence of Lipid Interactions.International journal of molecular sciences · 2023Review
- Critical role of synovial tissue-resident macrophage niche in joint homeostasis and suppression of chronic inflammation.Science advances · 2021Article
- Apoptosis, Autophagy, NETosis, Necroptosis, and Pyroptosis Mediated Programmed Cell Death as Targets for Innovative Therapy in Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Protozoan ParasiteFrontiers in microbiology · 2019Article
- Induction of immunosuppressive functions and NF-κB by FLIP in monocytes.Nature communications · 2018Article
- Intracellular apoptotic pathways: a potential target for reducing joint damage in rheumatoid arthritis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Review
- Deletion of c-FLIP from CD11bAmerican journal of respiratory cell and molecular biology · 2018Article
- The Role of Macrophages in the Response to TNF Inhibition in Experimental Arthritis.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Association of Increased F4/80Arthritis & rheumatology (Hoboken, N.J.) · 2017Article
- Expression of c-FLIP in a rat model of sepsis and its effects on endothelial apoptosis.Molecular medicine reports · 2017Article
- The inflammatory role of phagocyte apoptotic pathways in rheumatic diseases.Nature reviews. Rheumatology · 2016Review
- Fas Regulates Macrophage Polarization and Fibrogenic Phenotype in a Model of Chronic Ethanol-Induced Hepatocellular Injury.The American journal of pathology · 2016Article
- Adoptive Transfer of Dendritic Cells Expressing Fas Ligand Modulates Intestinal Inflammation in a Model of Inflammatory Bowel Disease.Journal of clinical & cellular immunology · 2016Article
- Apoptosis: role in myeloid cell development.Blood research · 2015Review
- Proteases in cardiometabolic diseases: Pathophysiology, molecular mechanisms and clinical applications.Biochimica et biophysica acta · 2015Review
- The Interplay Between Monocytes/Macrophages and CD4(+) T Cell Subsets in Rheumatoid Arthritis.Frontiers in immunology · 2015Review
- Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Macrophages differentiated from circulating peripheral blood monocytes are essential for host immune responses and have been implicated in the pathogenesis of rheumatoid arthritis and atherosclerosis. In contrast to monocytes, macrophages are resistant to Fas-induced cell death by an unknown mechanism. FLICE (Fas-associated death domain-like interleukin 1beta-converting enzyme)-inhibitory protein (Flip), a naturally occurring caspase-inhibitory protein that lacks the critical cysteine domain necessary for catalytic activity, is a negative regulator of Fas-induced apoptosis. Here, we show that monocyte differentiation into macrophages was associated with upregulation of Flip and a decrease in Fas-mediated apoptosis. Overexpression of Flip protected monocytes from Fas-mediated apoptosis, whereas acute Flip inhibition in macrophages induced apoptosis. Addition of an antagonistic Fas ligand antibody to Flip antisense-treated macrophages rescued cultures from apoptosis, demonstrating that endogenous Flip blocked Fas-induced cell death. Thus, the expression of Flip in macrophages conferred resistance to Fas-mediated apoptosis, which may contribute to the development of inflammatory disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.