Dual Specificity Phosphatases: From Molecular Mechanisms to Biological Function

Pulido, Rafael; Lang, Roland

doi:10.3390/ijms20184372

Cited by 17 publications

(13 citation statements)

References 25 publications

(26 reference statements)

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“…On the other hand, dephosphorylation of MAPKs is one of the most efficient mechanisms to control their activation. Dual specificity phosphatases (DUSP), also termed MKP can negatively regulate MAPKs activation through dephosphorylation of phosphotyrosine and phosphothreonine residues ( 24 ). DUSPs can be induced by TLR-mediated activation of MAPKs, creating a negative feedback loop to limit MAPKs activation.…”

Section: Discussionmentioning

confidence: 99%

Early p38 Activation Regulated by MKP-1 Is Determinant for High Levels of IL-10 Expression Through TLR2 Activation

et al. 2021

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Toll-like receptors (TLRs) play a crucial role in the recognition of pathogen-derived components as a first line of defense against infections. It has been suggested that depending on the nature of the pathogens, TLRs activation induce a distinct cytokine profile that may contribute to the polarization of the acquired immune response. Here, we investigated the early MAPK signaling activation via TLR4 and TLR2 receptors and its impact in differential cytokine profile by macrophages. We found that TLR2 ligands activated MAPKs p38 and ERK earlier compared to the TLR4 ligand LPS in macrophages. Higher IL-10/IL-12 and IL-10/TNF-α ratios were also observed at later time points in response to TLR2 ligands compared to LPS. The results also indicate an earlier activation of the phosphatase MKP-1 and that MKP-1 KO macrophages show a prolongation in p38 phosphorylation in response to TLR2 stimulation. Furthermore, p38 is critical for IL-10 expression in response to TLR2 ligands, which triggers the macrophage change to a M2 and regulatory phenotype in contrast to the M1 phenotype induced by TLR4 activation. Therefore, the early TLR2-mediated p38 induction contributes for the high IL-10 production, likely as a virulence strategy to suppress host Th1 response against certain types of pathogens.

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Section: Discussionmentioning

confidence: 99%

Early p38 Activation Regulated by MKP-1 Is Determinant for High Levels of IL-10 Expression Through TLR2 Activation

et al. 2021

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“…Molecular studies have indicated that Mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase (JNK), are involved in the inflammatory response and development of airway remodeling during childhood asthma ( Lee et al, 2019b ; Jia et al, 2019 ). Concretely, ERK1/2 is involved in airway remodeling ( Defnet et al, 2019 ), while p38 MAPK and JNK are considered as anti-inflammation targets to regulate inflammatory processes via phosphorylation of downstream mediators in childhood asthma ( Kim and Choi, 2010 ; Pulido and Lang, 2019 ; Theodorou et al, 2022 ). However, literatures about the pathogenesis of MAPK pathways in childhood asthma are limited.…”

Section: Asthma-associated Pathogenesismentioning

confidence: 99%

Emerging Roles of Non-Coding RNAs in Childhood Asthma

et al. 2022

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Asthma is a chronic airway inflammatory disease in children characterized by airway inflammation, airway hyperresponsiveness and airway remodeling. Childhood asthma is usually associated with allergy and atopy, unlike adult asthma, which is commonly associated with obesity, smoking, etc. The pathogenesis and diagnosis of childhood asthma also remains more challenging than adult asthma, such as many diseases showing similar symptoms may coexist and be confused with asthma. In terms of the treatment, although most childhood asthma can potentially be self-managed and controlled with drugs, approximately 5–10% of children suffer from severe uncontrolled asthma, which carries significant health and socioeconomic burdens. Therefore, it is necessary to explore the pathogenesis of childhood asthma from a new perspective. Studies have revealed that non-coding RNAs (ncRNAs) are involved in the regulation of respiratory diseases. In addition, altered expression of ncRNAs in blood, and in condensate of sputum or exhalation affects the progression of asthma via regulating immune response. In this review, we outline the regulation and pathogenesis of asthma and summarize the role of ncRNAs in childhood asthma. We also hold promise that ncRNAs may be used for the development of biomarkers and support a new therapeutic strategy for childhood asthma.

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“…Besides, dual-specificity phosphatase 6 (DUSP6) was reported to sponge miR-145-5p and thus further implicated in the regulation of chronic obstructive pulmonary disease [12]. DUSP, as a heterogeneous cluster of enzymes of the protein tyrosine phosphatase gene superfamily, is differentially expressed in resting and activated immune cells [13,14]. More importantly, DUSP6 was identified as a crucial player in the intervention of inflammatory bowel disease [15].…”

Section: Introductionmentioning

confidence: 99%

Short-Chain Fatty Acid Decreases the Expression of CEBPB to Inhibit miR-145-Mediated DUSP6 and Thus Further Suppresses Intestinal Inflammation

Liu

Peng²,

Zhou³

et al. 2021

Inflammation

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Intestinal inflammation is a common disease which can further lead to inflammatory bowel disease and even intestinal cancer. The increasing focus has come to the role of shortchain fatty acid (SCFA) in various bowel diseases. Hence, this study was designed to explore the specific role of SCFA in intestinal inflammation. In vivo and in vitro models of intestinal inflammation were constructed by lipopolysaccharide (LPS) injection in mice and LPS treatment on intestinal epithelial cells. A possible regulatory mechanism involving SCFA, CCAAT enhancerbinding protein beta (CEBPB), microRNA-145 (miR-145), and dual-specificity phosphatase 6 (DUSP6) in intestinal inflammation was verified by ChIP assay and dual-luciferase reporter gene assay. To evaluate the effects of SCFA on LPS-treated intestinal epithelial cells, the expression of relevant genes and inflammatory factors (IL-6, TNF-α, and IL-1β) were determined. Last, the role of SCFA in vivo was explored through the scoring of disease activity index (DAI) and observation of colonic histology of LPS-treated mice. SCFA decreased the CEBPB expression in mouse colon tissues and small intestine epithelial cells induced by LPS. Furthermore, CEBPB could bind to the miR-145 promoter to inhibit its expression, thereby promoting the expression of DUSP6. In addition, SCFA improved the DAI, colonic histology, and the expression of

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Dual Specificity Phosphatases: From Molecular Mechanisms to Biological Function

Abstract: Dual specificity phosphatases (DUSPs) constitute a heterogeneous group of enzymes, relevant in human disease, which belong to the class I Cys-based group of protein tyrosine phosphatase (PTP) gene superfamily [...]

Cited by 17 publications

References 25 publications

Early p38 Activation Regulated by MKP-1 Is Determinant for High Levels of IL-10 Expression Through TLR2 Activation

Early p38 Activation Regulated by MKP-1 Is Determinant for High Levels of IL-10 Expression Through TLR2 Activation

Emerging Roles of Non-Coding RNAs in Childhood Asthma

Short-Chain Fatty Acid Decreases the Expression of CEBPB to Inhibit miR-145-Mediated DUSP6 and Thus Further Suppresses Intestinal Inflammation

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