ArticlePloS one2014
TIPE2 negatively regulates inflammation by switching arginine metabolism from nitric oxide synthase to arginase.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- TIPE2 deficiency enhances macrophage phagocytosis of tumor cells.Journal for immunotherapy of cancer · 2025Article
- Beyond the Hit: Muscle and Vascular Tissue Responses to Contact Exposure in Collision Sports-A Narrative Review.Sports medicine (Auckland, N.Z.) · 2025Review
- Metabolic reprogramming of macrophages in chronic obstructive pulmonary disease.Frontiers in immunology · 2025Review
- Checkpoint TIPE2 Limits the Helper Functions of NK Cells in Supporting Antitumor CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Regulatory Roles of Tumor Necrosis Factor-α-Induced Protein 8 Like-Protein 2 in Inflammation, Immunity and Cancers: A Review.Cancer management and research · 2020Review
- Lipid Metabolic Pathways Confer the Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Tumor.Frontiers in immunology · 2019Review
- TNFAIP8: Inflammation, Immunity and Human Diseases.Journal of cellular immunology · 2019Article
- Ischemic postconditioning decreasesTranslational gastroenterology and hepatology · 2019Article
- TIPE Family of Proteins and Its Implications in Different Chronic Diseases.International journal of molecular sciences · 2018Review
- TIPE2 is negatively correlated with tissue factor and thrombospondin-1 expression in patients with bronchial asthma.Experimental and therapeutic medicine · 2018Article
- TIPE2 governs macrophage polarization via negative regulation of mTORC1.Molecular medicine reports · 2018Article
- TIPE3 protein promotes breast cancer metastasis through activating AKT and NF-κB signaling pathways.Oncotarget · 2017Article
- Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid transfer proteins.Cellular & molecular immunology · 2017Review
- Adenovirus-mediated TIPE2 overexpression inhibits gastric cancer metastasis via reversal of epithelial-mesenchymal transition.Cancer gene therapy · 2017Article
- Negative Immune Regulator TIPE2 Promotes M2 Macrophage Differentiation through the Activation of PI3K-AKT Signaling Pathway.PloS one · 2017Article
- Clinical Significance of TIPE2 Protein Upregulation in Non-Hodgkin's Lymphoma.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2016Article
- Adenovirus-directed expression of TIPE2 suppresses gastric cancer growth via induction of apoptosis and inhibition of AKT and ERK1/2 signaling.Cancer gene therapy · 2016Article
- TIPE2 regulates tumor-associated macrophages in skin squamous cell carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Metabolic reprogramming in macrophages and dendritic cells in innate immunity.Cell research · 2015Review
- MiR-21: an environmental driver of malignant melanoma?Journal of translational medicine · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TIPE2, the tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TNFAIP8L2), plays an essential role in maintaining immune homeostasis. It is highly expressed in macrophages and negatively regulates inflammation through inhibiting Toll-like receptor signaling. In this paper, we utilized RAW264.7 cells stably transfected with a TIPE2 expression plasmid, as well as TIPE2-deficient macrophages to study the roles of TIPE2 in LPS-induced nitric oxide (NO) and urea production. The results showed that TIPE2-deficiency significantly upregulated the levels of iNOS expression and NO production in LPS-stimulated macrophages, but decreased mRNA levels of arginase I and urea production. However, TIPE2 overexpression in macrophages was capable of downregulating protein levels of LPS-induced iNOS and NO, but generated greater levels of arginase I and urea production. Furthermore, TIPE2-/- mice had higher iNOS protein levels in lung and liver and higher plasma NO concentrations, but lower levels of liver arginase I compared to LPS-treated WT controls. Interestingly, significant increases in IκB degradation and phosphorylation of JNK, p38, and IκB were observed in TIPE2-deficient macrophages following LPS challenge. These results strongly suggest that TIPE2 plays an important role in shifting L-arginase metabolism from production of NO to urea, during host inflammatory response.
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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.