ArticleFrontiers in immunology2018
Receptor-Interacting Protein Kinases 1 and 3, and Mixed Lineage Kinase Domain-Like Protein Are Activated by Sublytic Complement and Participate in Complement-Dependent Cytotoxicity.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target.Nature reviews. Drug discovery · 2020Pooled it
- Thrombosis in paroxysmal nocturnal hemoglobinuria in the complement inhibitor era: mechanisms, risk stratification, and clinical management.International journal of hematology · 2026Review
- Complement system in tumor growth and metastases.British journal of cancer · 2026Review
- DJ-1 counteracts Caveolin-1-mediated necroptosis to inhibit epithelial barrier dysfunction in colitis.Cell death & disease · 2025Article
- Ficolin-3 Activates Complement and Triggers Necroptosis in Cholangiocarcinoma Cells via the RIPK1/RIPK3/MLKL Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- RIPK1 in necroptosis and recent progress in related pharmaceutics.Frontiers in immunology · 2025Review
- Targeting Necroptosis: A Novel Therapeutic Option for Retinal Degenerative Diseases.International journal of biological sciences · 2023Review
- Article
- The regulation of necroptosis and perspectives for the development of new drugs preventing ischemic/reperfusion of cardiac injury.Apoptosis : an international journal on programmed cell death · 2022Review
- A Novel Prognostic Predictor of Immune Microenvironment and Therapeutic Response in Kidney Renal Clear Cell Carcinoma based on Necroptosis-related Gene Signature.International journal of medical sciences · 2022Article
- Pharmacological modulation of myeloid-derived suppressor cells to dampen inflammation.Frontiers in immunology · 2022Review
- Complement membrane attack complex is an immunometabolic regulator of NLRP3 activation and IL-18 secretion in human macrophages.Frontiers in immunology · 2022Article
- Inducing regulated necrosis and shifting macrophage polarization with anti-EMMPRIN antibody (161-pAb) and complement factors.Journal of leukocyte biology · 2021Article
- Genetic inactivation of RIP1 kinase activity in rats protects against ischemic brain injury.Cell death & disease · 2021Article
- Article
- Complement Membrane Attack Complex: New Roles, Mechanisms of Action, and Therapeutic Targets.The American journal of pathology · 2020Review
- Pathomechanisms of Posttraumatic Osteoarthritis: Chondrocyte Behavior and Fate in a Precarious Environment.International journal of molecular sciences · 2020Review
- Angiotensin II triggers RIPK3-MLKL-mediated necroptosis by activating the Fas/FasL signaling pathway in renal tubular cells.PloS one · 2020Article
- Blowing epithelial cell bubbles with GumB: ShlA-family pore-forming toxins induce blebbing and rapid cellular death in corneal epithelial cells.PLoS pathogens · 2019Article
- Role of C5b-9 and RGC-32 in Cancer.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The complement system participates in the pathogenesis of many diseases. Complement activation produces several active protein complexes and peptides, including the terminal C5b-9 complexes. It was reported that C5b-9 complexes insert into the plasma membrane and cause membrane perturbation, intracellular calcium surge, metabolic depletion, and osmotic lysis. Previously, we showed that complement-dependent cytotoxicity (CDC) is regulated by JNK and Bid. Here, we demonstrate that three mediators in TNFα-induced necroptosis (regulated necrosis), the receptor-interacting protein kinases, receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein kinase 3 (RIPK3), and mixed-lineage kinase domain-like protein (MLKL), are activated by complement and contribute to CDC. Cell treatment with necrostatin-1 (Nec-1), a RIPK1 inhibitor, GSK'872, a RIPK3 inhibitor, or necrosulfonamide and GW806742X, MLKL inhibitors, restrain CDC. These findings were confirmed by using specific siRNAs targeting the synthesis of these proteins. Mouse fibroblasts lacking RIPK3 or MLKL were found to be less sensitive to C5b-9 than were wild-type (WT) fibroblasts. Enhanced CDC was achieved by RIPK1 or RIPK3 overexpression but not by the overexpression of a RHIM-RIPK1 mutant nor by a kinase-dead RIPK3 mutant. Nec-1 reduces the CDC of WT but not of RIPK3-knockout fibroblasts. Cells treated with a sublytic dose of complement exhibit co-localization of RIPK3 with RIPK1 in the cytoplasm and co-localization of RIPK3 and MLKL with C5b-9 at the plasma membrane. Data supporting cooperation among the RIP kinases, MLKL, JNK, and Bid in CDC are presented. These results provide a deeper insight into the cell death process activated by complement and identify potential points of cross talk between complement and other inducers of inflammation and regulated necrosis.
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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.