title: The inhibition of JNK and p38 MAPKs downregulates IL-10 and differentially affects c-Jun gene expression in human monocytes.
abstract: Interleukin-10 is the most important anti-inflammatory cytokine that controls the progress of the immune response. The molecular mechanisms driving the IL10 gene regulation are not well understood. To gain insight into this process we studied the IL-10 expression on mRNA and protein levels, together with c-Jun, FOXP3 and RelA transcription factors gene expression in human monocytes. We investigated also, the involvement of JNK and p38 transduction pathways in IL-10, c-Jun, FOXP3 and RelA gene expression. The quantity determination of IL-10 was performed by ELISA. qRT-PCR was performed for the detection of mRNA transcripts. The pharmacological inhibitors SP600125 and SB202190 were used to explore JNK and p38 MAPKs involvement in IL10, c-Jun, FOXP3 and RelA gene expression. The measurement of IL-10 mRNA synthesis, triggered by lipopolysaccharide (LPS) or C3 binding glycoprotein (C3bgp) showed that stimulation with both inducers led to similar high level of IL-10 mRNA synthesis, whereas C3bgp was the stronger inducer of IL-10 production than LPS. JNK and p38 inhibition significantly decreased IL-10 expression in stimulated cells. C3bgp and LPS induced comparatively low expression of FOXP3, RelA and c-Jun mRNA in monocytes. The inhibition of p38 MAPK in stimulated monocytes resulted in significant enhancement of c-Jun mRNA synthesis suggesting the functional relation between p38 MAPK and c-Jun gene expression. We concluded that the IL10 gene transcription did not associate with enhancement of c-Jun, RelA and FOXP3 gene expression and strictly depended on the JNK and p38 MAPKs activation in stimulated human monocytes.
authors.affiliation: Department of Molecular Biology, Immunology and Genetics, Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria. zdobreva@mf.uni-sz.bg
authors.forename: Zlatka Georgieva
authors.initials: ZG
authors.lastname: Dobreva
authors.forename: Lyuba Dineva
authors.initials: LD
authors.lastname: Miteva
authors.forename: Spaska Angelova
authors.initials: SA
authors.lastname: Stanilova
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009000:Monocytes / Q000201:enzymology / Q000276:immunology; D011725:Pyridines / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000235:genetics; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000873:Anthracenes; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007093:Imidazoles; D008070:Lipopolysaccharides; D011725:Pyridines; C498143:RELA protein, human; D051996:Transcription Factor RelA; D016753:Interleukin-10; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole