Journal ArticleDOI
The inhibition of JNK and p38 MAPKs downregulates IL-10 and differentially affects c-Jun gene expression in human monocytes
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TLDR
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.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.read more
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Effect of p38 MAPK inhibition on corticosteroid suppression of cytokine release in severe asthma
TL;DR: Coricosteroid insensitivity in severe asthma patients may be improved by inhibitors of p38 MAPK, and the concentration-dependent effects of another p38MAPK inhibitor, GW-A, on dexamethasone-induced inhibition of interleukin (IL)-8 release from PBMCs.
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Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome
TL;DR: Hypernitrosylation, as a consequence of chronically elevated O&NS and activated immune-inflammatory pathways, can explain many characteristic abnormalities observed in neuroprogressive disease including major depression and chronic fatigue syndrome/myalgic encephalomyelitis.
Journal ArticleDOI
IL-10 Receptor Signaling Is Essential for TR1 Cell Function In Vivo.
Leonie Brockmann,Nicola Gagliani,Babett Steglich,Anastasios D. Giannou,Jan Kempski,Penelope Pelczar,Maria Geffken,Bechara Mfarrej,Francis J. Huber,Johannes Herkel,Yisong Y. Wan,Enric Esplugues,Manuela Battaglia,Christian Krebs,Richard A. Flavell,Samuel Huber +15 more
TL;DR: TR1 cell regulatory activity is dependent on IL-10 receptor signaling, and data suggest that to optimize TR1 cell–based therapy, IL- 10 receptor expression has to be taken into consideration.
Journal ArticleDOI
Exposure to Traffic-Related Air Pollution and Serum Inflammatory Cytokines in Children.
Olena Gruzieva,Simon Kebede Merid,Anna Gref,Ashwini Gajulapuri,Nathanaël Lemonnier,Stephane Ballereau,Bruna Gigante,Juha Kere,Charles Auffray,Erik Melén,Erik Melén,Erik Melén,Göran Pershagen,Göran Pershagen +13 more
TL;DR: The results indicate alterations in systemic inflammatory markers in 8-y-old children in relation to early-life exposure to traffic-related air pollution, including IL10, IL13, and TNF.
Journal ArticleDOI
Influences of BRAF Inhibitors on the Immune Microenvironment and the Rationale for Combined Molecular and Immune Targeted Therapy
TL;DR: Additional translational studies are needed to better understand toxicity, proper timing, and sequence of therapy, as well as the utility of multidrug regimens and effects of other targeted agents on antitumor immunity.
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Steven M. Opal,Vera A. DePalo +1 more
TL;DR: The nature of anti- inflammatory cytokines and soluble cytokine receptors is the focus of this review and the current and future therapeutic uses of these anti-inflammatory cytokines are also reviewed.
Journal ArticleDOI
Endotoxin signal transduction in macrophages
Matthew J. Sweet,David A. Hume +1 more
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