Stefan Brocke

Cyclic nucleotide phosphodiesterases as drug targets

Michy P. Kelly, Viacheslav O. Nikolaev, Leila Gobejishvili, Claire Lugnier et autres

Cyclic nucleotides are synthesized by adenylyl and/or guanylyl cyclase, and downstream of this synthesis, the cyclic nucleotide phosphodiesterase families (PDEs) specifically hydrolyze cyclic nucleotides. PDEs control cyclic adenosine-3',5'monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) intracellular levels by mediating their quick return to the …

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Editorial: Cyclic Nucleotide Phosphodiesterases (PDEs) in Immune Regulation and Inflammation

Stefan Brocke, Paul M. Epstein, Robert M. Nelson, Tim Vanmierlo

Cyclic nucleotide phosphodiesterases (PDEs) in immune regulation and inflammationCyclic nucleotides are involved in many cellular functions and well-established regulator of immune responses and inflammation.Leukocytes play a critical role in inflammation and its modulation.Function and regulation of different subpopulations of T cells, B …

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Treatment of Experimental Autoimmune Encephalomyelitis with an Inhibitor of Phosphodiesterase-8 (PDE8)

Chaitali Basole, Rebecca Nguyen, Katie Lamothe, Puja Billis et autres

After decades of development, inhibitors targeting cyclic nucleotide phosphodiesterases (PDEs) expressed in leukocytes have entered clinical practice for the treatment of inflammatory disorders, with three PDE4 inhibitors being in clinical use as therapeutics for psoriasis, psoriatic arthritis, chronic obstructive pulmonary disease and …

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The Role of PDE8 in T Cell Recruitment and Function in Inflammation

Paul M. Epstein, Chaitali Basole, Stefan Brocke

Inhibitors targeting cyclic nucleotide phosphodiesterases (PDEs) expressed in leukocytes have entered clinical practice to treat inflammatory disorders, with three PDE4 inhibitors currently in clinical use as therapeutics for psoriasis, psoriatic arthritis, atopic dermatitis and chronic obstructive pulmonary disease. In contrast, the PDE8 …

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The differential roles of zinc in immune responses and their potential implications in antiviral immunity against SARS-CoV-2

Dirk Reinhold, Stefan Brocke

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Immunity to Respiratory Infection Is Reinforced Through Early Proliferation of Lymphoid TRM Cells and Prompt Arrival of Effector CD8 T Cells in the Lungs

Jenny E Suarez-Ramirez, Karthik Chandiran, Stefan Brocke, Linda S. Cauley

Cross-protection between serologically distinct strains of influenza A virus (IAV) is mediated by memory CD8 T cells that recognize epitopes from conserved viral proteins. Early viral control begins with activation of tissue-resident memory CD8 T cells (TRM) cells at the site of …

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P058 Phosphodiesterase 8A domains at the site of leucocyte–endothelial cell adhesion in ulcerative colitis submucosa

N Ovadóttir, Karen Vagner Danielsen, Kári Rubek Nielsen, Paul M. Epstein et autres

Development of anti-adhesion therapies like Etrolizumab and Alicaforsen highlights the potential for inhibiting recruitment pathways in ulcerative colitis (UC). Recent in vitro mouse work from our group shows that disruption of Phosphodiesterase (PDE) 8A domains inhibits T cell adhesion to ICAM-1 and …

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PDE8 controls CD4+ T cell motility through the PDE8A-Raf-1 kinase signaling complex

Chaitali Basole, Rebecca Nguyen, Katie Lamothe, Amanda Vang et autres

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Differential Expression and Function of PDE8 and PDE4 in Effector T cells: Implications for PDE8 as a Drug Target in Inflammation

Amanda Vang, Chaitali Basole, Hongli Dong, Rebecca Nguyen et autres

Abolishing the inhibitory signal of intracellular cAMP is a prerequisite for effector T (Teff) cell function. The regulation of cAMP within leukocytes critically depends on its degradation by cyclic nucleotide phosphodiesterases (PDEs). We have previously shown that PDE8A, a PDE isoform with …

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Targeting the PDE8A-Raf-1 kinase signaling complex to treat autoimmune inflammation

Chaitali P Basole, Rebecca Nguyen, Katie Lamothe, Amanda Vang et autres

Abstract The levels of cAMP are regulated by phosphodiesterases (PDE), which are targets for the treatment of inflammatory disorders. We previously showed that PDE8A regulates T cell motility. We report here that PDE8A exerts its control of T cell function through the …

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Inhibition of breast cancer cell migration by activation of cAMP signaling

Hongli Dong, Kevin P. Claffey, Stefan Brocke, Paul M. Epstein

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Oral zinc aspartate treats experimental autoimmune encephalomyelitis

Claudia Schubert, Karina Guttek, Kurt Grüngreiff, Anja Thielitz et autres

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