ArticleInfection and immunity2015
Transforming growth factor β2 promotes transcription of COX2 and EP4, leading to a prostaglandin E2-driven autostimulatory loop that enhances virulence of Theileria annulata-transformed macrophages.
Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Epigenetic landscape of the H3K27me3 mark in macrophages transformed by Theileria annulata.Communications biology · 2026Article
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Glucocorticoids in lung cancer: Navigating the balance between immunosuppression and therapeutic efficacy.Heliyon · 2024Review
- The interplay of cytokines in bovine tropical theileriosis: a mini review.Tropical animal health and production · 2024Review
- TFF3 promotes clonogenic survival of colorectal cancer cells through upregulation of EP4 via activation of STAT3.Translational cancer research · 2023Article
- Article
- cAMP-Dependent Signaling Pathways as Potential Targets for Inhibition ofFrontiers in microbiology · 2021Review
- Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells.Cellular microbiology · 2020Article
- Repurposing Auranofin and Evaluation of a New Gold(I) Compound for the Search of Treatment of Human and Cattle Parasitic Diseases: From Protozoa to Helminth Infections.Molecules (Basel, Switzerland) · 2020Article
- Bovine piroplasmosis-anaplasmosis and clinical signs of tropical theileriosis in the plains of Djurdjura (north Algeria).Veterinary medicine and science · 2020Article
- Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor.Scientific reports · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Cell penetrating peptides to dissect host-pathogen protein-protein interactions in Theileria-transformed leukocytes.Bioorganic & medicinal chemistry · 2018Review
- Xanthine dehydrogenase downregulation promotes TGFβ signaling and cancer stem cell-related gene expression in hepatocellular carcinoma.Oncogenesis · 2017Article
- Modulation of cyclic nucleotide-mediated cellular signaling and gene expression using photoactivated adenylyl cyclase as an optogenetic tool.Scientific reports · 2017Article
- PKA and Apicomplexan Parasite Diseases.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2017Review
- HK2 Recruitment to Phospho-BAD Prevents Its Degradation, Promoting Warburg Glycolysis by Theileria-Transformed Leukocytes.ACS infectious diseases · 2017Article
- Potential Sabotage of Host Cell Physiology by Apicomplexan Parasites for Their Survival Benefits.Frontiers in immunology · 2017Review
- Exchange factors directly activated by cAMP mediate melanocortin 4 receptor-induced gene expression.Scientific reports · 2016Article
- TGF-β2 induces Grb2 to recruit PI3-K to TGF-RII that activates JNK/AP-1-signaling and augments invasiveness of Theileria-transformed macrophages.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor beta (TGF-β) is a pleiotropic cytokine known to regulate cell growth, differentiation, and motility and is a potent modulator of immune function. TGF-β consequently plays a central role in carcinogenesis, and a dampened TGF-β2 response by Theileria annulata-infected monocytes/macrophages underpins disease resistance to tropical theileriosis. Here, we show that concomitant with the loss of TGF-β2 production, there is ablated expression of COX2 and EP4, which leads to a drop in cyclic AMP (cAMP) levels and, consequently, reduced activation of protein kinase A (PKA) and EPAC. This ablated phenotype can be rescued in attenuated macrophages by the addition of exogenous TGF-β2, which reactivates the expression of COX2 and EP4 while repressing that of protein kinase inhibitor gamma (PKIG) to the levels in virulent macrophages. TGF-β2 therefore promotes the adhesion and invasiveness of virulent macrophages by modulating COX2, EP4, and PKIG transcription to initiate a prostaglandin E2 (PGE2)-driven autostimulatory loop that augments PKA and EPAC activities. A virulence phenotype stemming from the double activation of PKA and EPAC is the induction of a CREB-mediated transcriptional program and the upregulation of JAM-L- and integrin 4αβ1-mediated adhesion of Theileria-infected macrophages.
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