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Published on: October 13, 2013
Interaction between oncostatin M, interleukin 1 and prostaglandin E2 in induction of IL-6 expression in human
1Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Abstract:
The role of Oncostatin M (OM), a monocyte/macrophage and T-cell product, in regulating IL-6 expression in fibroblasts of lung or synovial origin was examined in vitro. Although by itself OM had a minimal effect on enhancing IL-6 production by fibroblasts, in combination with IL-1 alpha or PGE2, OM addition resulted in a dose-dependent synergistic enhancement of IL-6 production. This synergistic effect with either IL-1 alpha (5 ng/ml) or PGE2 (10(-7) M) was clearly evident at concentrations of OM of 10, 20 or 50 ng/ml. Levels of IL-6 resulting from OM and IL-1 alpha stimulation could be reduced by indomethacin (10(-6) M) and restored again by also adding PGE2. Northern blots probed for IL-6 mRNA showed cooperative enhancement of steady state levels at 18 hours of stimulation by OM and IL-1 alpha, or OM and PGE2. Probing for mRNA of the metalloproteinase inhibitor TIMP-1 showed that stimulation by OM, IL-1 alpha or PGE2 enhanced TIMP-1 levels. However, OM (alone) or PGE2 or both combined did not elevate the metalloproteinase stromelysin-1 mRNA signals. Analysis utilizing a rat IL-6 promoter-luciferase reporter gene construct showed that OM stimulation resulted in activation of transcription that synergistically enhanced IL-1-induced levels of reporter gene expression. These results show that although OM has minor effects on IL-6 production alone, the combination of OM and other mediators result in markedly enhanced IL-6 production by fibroblasts in vitro.
Insights
Oncostatin M (OM) minimally impacts IL-6 production alone. However, OM synergistically enhances IL-6 expression in fibroblasts when combined with IL-1 alpha or PGE2, impacting inflammatory responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Oncostatin M (OM) is a cytokine produced by monocytes, macrophages, and T-cells.
- Interleukin-6 (IL-6) is a key inflammatory cytokine.
- Fibroblasts play a role in tissue repair and inflammation.
Purpose of the Study:
- To investigate the role of Oncostatin M (OM) in regulating Interleukin-6 (IL-6) expression in lung and synovial fibroblasts.
- To determine if OM synergizes with other inflammatory mediators to enhance IL-6 production.
Main Methods:
- In vitro cell culture of fibroblasts.
- Stimulation with Oncostatin M (OM), IL-1 alpha, and Prostaglandin E2 (PGE2).
- Measurement of IL-6 production via ELISA and mRNA levels via Northern blot.
- Analysis of gene transcription using a rat IL-6 promoter-luciferase reporter construct.
Main Results:
- OM alone had minimal effect on IL-6 production.
- OM synergistically enhanced IL-6 production in combination with IL-1 alpha or PGE2 in a dose-dependent manner.
- OM, IL-1 alpha, and PGE2 enhanced TIMP-1 mRNA levels, but not stromelysin-1 mRNA.
- OM stimulation activated transcription, synergistically enhancing IL-1-induced reporter gene expression.
Conclusions:
- Oncostatin M (OM) plays a significant role in potentiating IL-6 production by fibroblasts, particularly in the presence of other inflammatory mediators like IL-1 alpha and PGE2.
- The synergistic effect of OM on IL-6 production involves transcriptional activation.
- These findings highlight the complex interplay of cytokines in regulating fibroblast-mediated inflammatory responses.
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