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Interleukin-1 release by rat synovial cells is dependent on sequential treatment with gamma-interferon and
W J Johnson1, J Breton, T Newman-Tarr
1Department of Immunology, Smith Kline & French Laboratories, King of Prussia, PA 19406-0939.
Insights
Gamma-interferon (gamma-IFN) primes rat synovial cells, enabling lipopolysaccharide (LPS) to induce interleukin-1 (IL-1) release. This sequential stimulation is crucial for regulating IL-1 production in these cells.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Interleukin-1 (IL-1) is a key cytokine involved in inflammatory processes.
- Synovial cells play a critical role in joint inflammation and immune responses.
- Mechanisms regulating IL-1 release from synovial cells are not fully understood.
Purpose of the Study:
- To investigate the role of gamma-interferon (gamma-IFN) in regulating interleukin-1 (IL-1) release from rat synovial cells.
- To elucidate the signaling pathways involved in gamma-IFN-mediated IL-1 induction.
Main Methods:
- Rat synovial cells were cultured and treated with various stimuli, including gamma-interferon (gamma-IFN) and lipopolysaccharide (LPS).
- Interleukin-1 (IL-1) levels were measured intracellularly and extracellularly.
- Messenger RNA (mRNA) induction for IL-1 was assessed.
- Ia antigen expression was monitored.
Main Results:
- Gamma-interferon (gamma-IFN) alone did not induce IL-1 release.
- Pretreatment with gamma-IFN followed by lipopolysaccharide (LPS) stimulation significantly increased intracellular IL-1 and IL-1 release.
- IL-1 release was dependent on the concentrations of gamma-IFN and LPS, and exposure time.
- LPS was essential for IL-1 mRNA induction, intracellular accumulation, and release.
- Sequential treatment (gamma-IFN then LPS) was critical for IL-1 induction.
Conclusions:
- Gamma-interferon (gamma-IFN) acts as a priming signal for rat synovial cells.
- Lipopolysaccharide (LPS) stimulation is required for subsequent IL-1 induction and release.
- These findings highlight a novel regulatory mechanism for IL-1 release involving sequential cytokine signaling.
Abstract:
To determine the potential regulatory mechanisms involved in synovial cell interleukin-1 (IL-1) release, the ability of gamma-interferon (gamma-IFN) to influence IL-1 release was assessed. Rat synovial cells cultured in the presence of a variety of stimuli, including lipopolysaccharide (LPS), failed to release IL-1. However, pretreatment of synovial cells with gamma-IFN, followed by LPS stimulation, resulted in increased levels of intracellular IL-1 as well as release of IL-1 from the cell. The level of IL-1 release was dependent on the concentration of both gamma-IFN and LPS, and on length of exposure to the gamma-IFN. The kinetic and dose requirements for gamma-IFN-dependent IL-1 release were similar to those for Ia antigen expression, but LPS was necessary for IL-1 messenger RNA induction, intracellular IL-1 accumulation, and IL-1 release. In addition, sequential treatment, i.e., gamma-IFN followed by LPS, was essential for IL-1 induction. Substitution of phorbol ester or calcium ionophore for gamma-IFN did not result in similar IL-1 release. In addition, induction of IL-1 messenger RNA by another stimulus was not sufficient to result in IL-1 release following LPS treatment. These results suggest that release of IL-1 by rat synovial cells requires the production of a regulatory signal, which is inducible by gamma-IFN.