<scp>PDE</scp>4 inhibitor rolipram inhibits the expression of microsomal prostaglandin E synthase‐1 by a mechanism dependent on <scp>MAP</scp> kinase phosphatase‐1

Tuure, Lauri; Hämäläinen, Mari; Moilanen, Eeva

doi:10.1002/prp2.363

Cited by 3 publications

(1 citation statement)

References 47 publications

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“…The promoter region of MKP-1 gene contains binding cites for several transcription factors, including activator protein 1 (AP-1), NF-κB, cAMP response element-binding protein (CREB) in addition to the glucocorticoid-responsive element (GRE) [ 15 ]. Accordingly, several other anti-inflammatory drugs, such as β2-receptor agonists, phosphodiesterase 4 (PDE4) inhibitors and aurothiomalate, have also been shown to enhance MKP-1 expression [ 18 , 19 , 20 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1

Lehtola

Nummenmaa

Tuure

et al. 2022

IJMS

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Mitogen-activated protein kinase phosphatase-1 (MKP-1) is upregulated in inflammation and reduces the activity of proinflammatory mitogen-activated protein kinases (MAP kinases) by dephosphorylation. MAP kinases are intracellular signaling pathways that mediate the cellular effects of proinflammatory cytokines. In the present study, we investigated the effects of the glucocorticoid dexamethasone on the expression of catabolic enzymes in chondrocytes and tested the hypothesis that these effects are mediated through MKP-1. Dexamethasone was found to significantly attenuate the expression of matrix metalloproteinase (MMP)-13 in human OA chondrocytes as well as in chondrocytes from MKP-1 WT mice, but not in chondrocytes from MKP-1 KO mice. Dexamethasone also increased the expression of MKP-1 in murine and human OA chondrocytes. Furthermore, p38 MAP kinase inhibitors significantly attenuated MMP-13 expression in human OA chondrocytes, while JNK MAP kinase inhibitors had no effect. The results indicate that the effect of dexamethasone on MMP-13 expression in chondrocytes was mediated by an MKP-1 and p38 MAP kinase-dependent manner. These findings, together with previous results, support the concept of MKP-1 as a protective factor in articular chondrocytes in inflammatory conditions and as a potential drug target to treat OA.

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Section: Discussionmentioning

confidence: 99%

Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1

Lehtola

Nummenmaa

Tuure

et al. 2022

IJMS

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Exploratory Study of Differentially Expressed Genes of Peripheral Blood Monocytes in Patients with Carotid Atherosclerosis

Chen,

Xu,

et al. 2024

CCHTS

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Background: The abundance of circulating monocytes is closely associated with the development of atherosclerosis in humans. Objective: This study aimed to further research into diagnostic biomarkers and targeted treatment of carotid atherosclerosis (CAS). Methods: We performed transcriptomics analysis through weighted gene co-expression network analysis (WGCNA) of monocytes from patients in public databases with and without CAS. Differentially expressed genes (DEGs) were screened by R package limma. Diagnostic molecules were derived by the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithms. NetworkAnalyst, miRWalk, and StarBase databases assisted in the construction of diagnostic molecule regulatory networks. The DrugBank database predicted drugs targeting the diagnostic molecules. RT-PCR tested expression profiles. Results: From 14,369 hub genes and 61 DEGs, six differentially expressed monocyte-related hub genes were significantly associated with immune cells, immune responses, monocytes, and lipid metabolism. LASSO and SVM-RFE yielded five genes for CAS prediction. RT-PCR of these genes showed HMGB1 was upregulated, and CCL3, CCL3L1, CCL4, and DUSP1 were down-regulated in CAS versus controls. Then, we constructed and visualized the regulatory networks of 9 transcription factors (TFs), which significantly related to 5 diagnostic molecules. About 11 miRNAs, 19 lncRNAs, and 39 edges centered on four diagnostic molecules (CCL3, CCL4, DUSP1, and HMGB1) were constructed and displayed. Eleven potential drugs were identified, including ibrutinib, CTI-01, roflumilast etc. Conclusion: A set of five biomarkers were identified for the diagnosis of CAS and for the study of potential therapeutic targets.

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Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection

Risner

Ahmed

Bakovic

et al. 2019

Viruses

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Venezuelan equine encephalitis virus (VEEV) is a category B select agent pathogen that can be aerosolized. Infections in murine models and humans can advance to an encephalitic phenotype which may result in long-term neurological complications or death. No specific FDA-approved treatments or vaccines are available for the treatment or prevention of VEEV infection. Neurotropic viral infections have two damaging components: neuronal death caused by viral replication, and damage from the subsequent inflammatory response. Reducing the level of inflammation may lessen neurological tissue damage that often arises following VEEV infection. In this study, three commercially available anti-inflammatory drugs, Celecoxib, Rolipram, and Tofacitinib, were evaluated for antiviral activity in an astrocyte and a microglial model of VEEV infection. The inhibitors were tested against the vaccine strain VEEV TC-83, as well as the wild-type VEEV Trinidad donkey strain. Celecoxib, Tofacitinib, and Rolipram significantly decreased viral titers both after pre-treatment and post-treatment of infected cells. VEEV Trinidad Donkey (TrD) titers were reduced 6.45-fold in cells treated with 50 µM of Celecoxib, 2.45-fold when treated with 50 µM of Tofacitinib, and 1.81-fold when treated with 50 µM of Rolipram. Celecoxib was also shown to decrease inflammatory gene expression in the context of TC-83 infection. Overall, Celecoxib demonstrated potency as a countermeasure strategy that slowed VEEV infection and infection-induced inflammation in an in vitro model.

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PDE4 inhibitor rolipram inhibits the expression of microsomal prostaglandin E synthase‐1 by a mechanism dependent on MAP kinase phosphatase‐1

Cited by 3 publications

References 47 publications

Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1

Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1

Exploratory Study of Differentially Expressed Genes of Peripheral Blood Monocytes in Patients with Carotid Atherosclerosis

Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection

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