Mitogen-activated protein kinase pathway controls autoimmune regulator () gene expression in granulo-monocyte colony stimulating factor (GM-CSF)-stimulated myelomonocytic leukemia OTC-4 cells

2005 ◽  
Vol 99 (1) ◽  
pp. 130-135 ◽  
Author(s):  
S NAGAFUCHI ◽  
H KATSUTA ◽  
Y OHNO ◽  
Y INOUE ◽  
K SHIMODA ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Regulator Gene ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Mitogen Activated Protein ◽  
Myelomonocytic Leukemia ◽  
Kinase Pathway ◽  
Stimulating Factor

scholarly journals Whole Genome Microarray Analysis of DUSP4-Deletion Reveals A Novel Role for MAP Kinase Phosphatase-2 (MKP-2) in Macrophage Gene Expression and Function

2019 ◽  
Vol 20 (14) ◽  
pp. 3434 ◽  
Author(s):  
Thikryat Neamatallah ◽  
Shilan Jabbar ◽  
Rothwelle Tate ◽  
Juliane Schroeder ◽  
Muhannad Shweash ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Whole Genome ◽  
Colony Stimulating Factor ◽  
Wild Type ◽  
Macrophage Function ◽  
Mitogen Activated Protein ◽  
Whole Genome Microarray ◽  
Stimulating Factor

Background: Mitogen-activated protein kinase phosphatase-2 (MKP-2) is a type 1 nuclear dual specific phosphatase (DUSP-4). It plays an important role in macrophage inflammatory responses through the negative regulation of Mitogen activated protein kinase (MAPK) signalling. However, information on the effect of MKP-2 on other aspect of macrophage function is limited. Methods: We investigated the impact of MKP-2 in the regulation of several genes that are involved in function while using comparative whole genome microarray analysis in macrophages from MKP-2 wild type (wt) and knock out (ko) mice. Results: Our data showed that the lack of MKP-2 caused a significant down-regulation of colony-stimulating factor-2 (Csf2) and monocyte to macrophage-associated differentiation (Mmd) genes, suggesting a role of MKP-2 in macrophage development. When treated with macrophage colony stimulating factor (M-CSF), Mmd and Csf2 mRNA levels increased but significantly reduced in ko cells in comparison to wt counterparts. This effect of MKP-2 deletion on macrophage function was also observed by cell counting and DNA measurements. On the signalling level, M-CSF stimulation induced extracellular signal-regulated kinases (ERK) phosphorylation, which was significantly enhanced in the absence of MKP-2. Pharmacological inhibition of ERK reduced both Csf2 and Mmd genes in both wild type and ko cultures, which suggested that enhanced ERK activation in ko cultures may not explain effects on gene expression. Interestingly other functional markers were also shown to be reduced in ko macrophages in comparison to wt mice; the expression of CD115, which is a receptor for M-CSF, and CD34, a stem/progenitor cell marker, suggesting global regulation of gene expression by MKP-2. Conclusions: Transcriptome profiling reveals that MKP-2 regulates macrophage development showing candidate targets from monocyte-to-macrophage differentiation and macrophage proliferation. However, it is unclear whether effects upon ERK signalling are able to explain the effects of DUSP-4 deletion on macrophage function.

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