Role and regulation of MKP-1 in airway inflammation

Moosavi, Seyed Mostafa Shid; Prabhala, Pavan; Ammit, Alaina J.

doi:10.1186/s12931-017-0637-3

Cited by 39 publications

(30 citation statements)

References 119 publications

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“…Glucocorticoid receptor-mediated MKP-1 signaling is a key process in the regulation of steroid resistance and sensitivity (30). The MKP-1 gene promoter region contains binding sites for several transcription factors, such as activator protein 1 (AP-1), AP-2, vitamin D receptor element and GRE (31). In the present study, IL-35 + DEX induced a significantly higher MKP-1 mRNA expression level in patients with SS asthma compared with those with SR asthma, which is consistent with the present p-p38 MAPK data.…”

Section: Discussionmentioning

confidence: 99%

Interleukin‑35 sensitizes monocytes from patients with asthma to glucocorticoid therapy by regulating p38 MAPK

Qian

Xue

et al. 2020

Exp Ther Med

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The activation of monocytes and macrophages is associated with steroid-resistant (SR) asthma. Interleukin-35 (IL-35) is an important anti-inflammatory cytokine, but its regulatory effects on monocytes in patients with SR asthma is not fully understood. Based on clinical response to oral prednisolone, 34 patients with steroid-sensitive (SS) asthma and 20 patients with SR asthma were enrolled in the present study. Serum IL-35 levels were analyzed using the Luminex 200 platform. Monocytes from patients with asthma were pretreated with IL-35 followed by dexamethasone (DEX) and lipopolysaccharide (LPS), then corticosteroid sensitivity was evaluated according to the half-maximal inhibitory concentration of DEX with respect to LPS-induced IL-6 maximal production in monocytes (DEX-IC 50). The percentage of maximal inhibition of IL-6 by DEX was presented as E max. Phosphorylated-P38 mitogen activated kinase (p-p38 MAPK) and mitogen-activated protein kinase phosphatase-1 (MKP-1) were examined by flow cytometry and reverse transcription-quantitative PCR analysis, respectively. Glucocorticoid receptor (GR) binding to the glucocorticoid response element (GRE) was assessed by chromatin immunoprecipitation. Compared with patients with SS asthma, patients with SR asthma had lower IL-35 expression levels (P<0.05). Correlation analysis results demonstrated that the expression levels of IL-35 showed a weak negative correlation with log DEX-IC 50 (r=-0.351; P<0.01) and a moderate positive correlation with E max value (r=0.4501; P<0.01) in all patients with asthma. Moreover, IL-35 enhanced DEX-suppressed IL-6 production and the DEX-induced upregulation of the MKP-1 mRNA expression level in monocytes from both patient groups (P<0.01). In addition, IL-35 inhibited p-p38 MAPK expression in monocytes, and these effects were mediated via an increase in DEX-induced GR binding to GRE. Therefore, IL-35 may be involved in the corticosteroid enhancing effects in monocytes of patients with SR and SS asthma, suggesting potential benefits of IL-35 supplementation in asthmatics with DEX.

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Section: Discussionmentioning

confidence: 99%

Interleukin‑35 sensitizes monocytes from patients with asthma to glucocorticoid therapy by regulating p38 MAPK

Qian

Xue

et al. 2020

Exp Ther Med

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“…Sustained activation of ERK phosphorylates DUSP1 on Ser296 and Ser323 residues [54]. The Ser296/323 phosphorylation of DUSP1 facilitates its interaction with the ubiquitin E3 ligase CUL1/SKP2/CKS1 complex, which targets DUSP1 for proteasomal degradation [27,54,55]. In contrast, ERK reduces DUSP1 degradation by phosphorylating two other residues, Ser359 and Ser364 [56,57].…”

Section: Other Post-translational Regulations Of Dusp Ubiquitinatimentioning

confidence: 99%

Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability

Chen

Chuang

Tan

2019

IJMS

132

109

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Mitogen-activated protein kinases (MAPKs) are key regulators of signal transduction and cell responses. Abnormalities in MAPKs are associated with multiple diseases. Dual-specificity phosphatases (DUSPs) dephosphorylate many key signaling molecules, including MAPKs, leading to the regulation of duration, magnitude, or spatiotemporal profiles of MAPK activities. Hence, DUSPs need to be properly controlled. Protein post-translational modifications, such as ubiquitination, phosphorylation, methylation, and acetylation, play important roles in the regulation of protein stability and activity. Ubiquitination is critical for controlling protein degradation, activation, and interaction. For DUSPs, ubiquitination induces degradation of eight DUSPs, namely, DUSP1, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8, DUSP9, and DUSP16. In addition, protein stability of DUSP2 and DUSP10 is enhanced by phosphorylation. Methylation-induced ubiquitination of DUSP14 stimulates its phosphatase activity. In this review, we summarize the knowledge of the regulation of DUSP stability and ubiquitination through post-translational modifications.

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“…These phosphatases inactivate mitogen-activated protein (MAP) kinases that have essential roles in cell proliferation and expression of cytokine genes. As an example protein phosphatase MKP-1 dephosphorylates and inactivates stress-activated protein kinases p38 and JNK (Moosavi, Prabhala, & Ammit, 2017). Therefore, ROS normally enable the transient, reversible activation of MAP kinases, which allows the cell to return to kinase basal activity within a given time frame after stimulation (Irani, Herzlinger, & Finkel, 1994; Sundaresan, Yu, Ferrans, Irani,& Finkel, 1995).…”

Section: Molecular Drivers Of Inflammation-induced Signaling In Lung mentioning

confidence: 99%

Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung cancer

Vlahopoulos

Adamaki

Khoury

et al. 2019

Pharmacology & Therapeutics

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Cytokines are pivotal mediators of the immune response, and their coordinated expression protects host tissue from excessive damage and oxidant stress. Nevertheless, the development of lung pathology, including asthma, chronic obstructive pulmonary disease, and ozone-induced lung injury, is associated with oxidant stress; as evidence, there is a significant increase in levels of the modified guanine base 7,8-dihydro-8-oxoguanine (8-oxoG) in the genome. 8-OxoG is primarily recognized by 8-oxoguanine glycosylase 1 (OGG1), which catalyzes the first step in the DNA base excision repair pathway. However, oxidant stress in the cell transiently halts enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, including NF-κB, to their cognate sites to enable expression of cytokines and chemokines, with ensuing recruitments of inflammatory cells. Hence, defective OGG1 will modulate the coordination between innate and adaptive immunity through excessive oxidant stress and cytokine dysregulation. Both oxidant stress and cytokine dysregulation constitute key elements of oncogenesis by KRAS, which is mechanistically coupled to OGG1. Thus, analysis of the mechanism by which OGG1 modulates gene expression helps discern between beneficial and detrimental effects of oxidant stress, exposes a missing functional link as a marker, and yields a novel target for lung cancer.

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Role and regulation of MKP-1 in airway inflammation

Cited by 39 publications

References 119 publications

Interleukin‑35 sensitizes monocytes from patients with asthma to glucocorticoid therapy by regulating p38 MAPK

Interleukin‑35 sensitizes monocytes from patients with asthma to glucocorticoid therapy by regulating p38 MAPK

Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability

Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung cancer

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