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Effect of recombinant interleukin-1beta on murine CD14 gene expression in vivo
1Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Abstract:
Recombinant murine interleukin-1beta (IL-1beta) induced a transient increase in plasma levels of CD14 with a peak at 8 h, and this increase in plasma CD14 antigen was accompanied by increased levels of CD14 messenger ribonucleic acid (mRNA) in all organs examined. In most organs, maximal levels of induction were obtained after administration of 125 ng of IL-1beta. Moreover, in situ hybridization studies revealed that CD14 mRNA was induced in both myeloid cells and epithelial cells. Pretreatment of mice with anti-lL-1beta antibodies reduced the subsequent induction of plasma levels of CD14 by lipopolysaccharide (LPS) and significantly reduced the level of induction of CD14 mRNA in kidney and liver. The antibodies did not block LPS mediated induction in lung. Pretreatment with a combination of anti-lL-1beta and anti-tumor necrosis factor (TNF) antibodies was more effective in reducing LPS mediated induction of plasma CD14 and CD14 mRNA in liver than pretreatment with either antibody alone. The combination of anti-lL-1beta and anti-TNF antibodies had no additional effect in kidney and lung over that observed with anti-TNF alone. These studies demonstrate that regulation of CD14 gene expression by LPS in vivo involves multiple signals but is mediated, in part, by the cytokines IL-1beta and TNF-alpha.
Insights
Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) cytokines regulate CD14 gene expression. Lipopolysaccharide (LPS) induction of CD14 involves multiple signaling pathways, including these key cytokines.
Area of Science:
- Immunology
- Molecular Biology
- Gene Expression Regulation
Background:
- CD14 is a key receptor involved in innate immunity.
- Lipopolysaccharide (LPS) is a potent activator of immune responses.
- The regulatory mechanisms of CD14 gene expression in vivo are not fully understood.
Purpose of the Study:
- To investigate the role of interleukin-1beta (IL-1beta) in regulating CD14 expression.
- To determine the involvement of IL-1beta and tumor necrosis factor-alpha (TNF-alpha) in LPS-induced CD14 expression.
- To elucidate the signaling pathways mediating CD14 gene regulation by LPS.
Main Methods:
- Recombinant murine IL-1beta administration to mice.
- Measurement of plasma CD14 levels.
- Quantification of CD14 messenger RNA (mRNA) in various organs using in situ hybridization.
- Administration of anti-IL-1beta and anti-TNF-alpha antibodies prior to LPS challenge.
Main Results:
- Recombinant IL-1beta induced transient increases in plasma CD14 and CD14 mRNA levels in multiple organs.
- CD14 mRNA induction by IL-1beta was observed in both myeloid and epithelial cells.
- Anti-IL-1beta antibodies partially reduced LPS-induced CD14 expression in kidney and liver, but not lung.
- Combined anti-IL-1beta and anti-TNF-alpha antibodies were more effective than single antibodies in reducing LPS-induced CD14 expression in the liver.
Conclusions:
- LPS-mediated regulation of CD14 gene expression in vivo involves multiple signaling pathways.
- IL-1beta and TNF-alpha are key cytokines that partially mediate LPS-induced CD14 expression.
- Tissue-specific differences exist in the cytokine-mediated regulation of CD14 by LPS.