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Expression of cytokine mRNA in extrahepatic organs in a mouse concanavalin A-hepatitis model
T Okamoto1, Y Nakano, W Asakura
1Research Laboratories, Nippon Chemiphar Co., Ltd., Misato, Saitama, Japan.
Abstract:
The liver injury in the concanavalin A (Con A)-induced mouse hepatitis model has been well studied. However, there has been little study on the effects of Con A on extrahepatic organs. The aim of the present work was to determine the effects of Con A on the spleen, kidney and lung. A histopathological study showed that Con A (15 mg/kg, i.v.) administration affects not only the liver, but also all these extrahepatic organs. Messenger RNA expression was studied by the using polymerase chain reaction. Treatment with Con A induced interleukin-2 mRNA in the spleen, but only slightly induced it in the kidney. The mRNAs of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were induced in all these organs. At 24 hr after Con A treatment, the expression of IFN-gamma mRNA, but not that of TNF-alpha mRNA, was inhibited by cyclosporine A (50 mg/kg, i.p.), suggesting that Con A induced these cytokine mRNAs through different mechanisms. In the kidney and lung, CD4+ and CD8+ T-cell infiltration was suggested by the Con A-induced CD4 and CD8 mRNAs. The present study showed the histopathological effects of Con A and Con A-induced cytokine mRNA expression on the spleen, kidney and lung.
Insights
Concanavalin A (Con A) causes liver injury and also affects the spleen, kidney, and lung. Con A induces cytokine messenger RNA (mRNA) in these organs, indicating widespread inflammation beyond the liver.
Area of Science:
- Immunology
- Toxicology
- Pathology
Background:
- The concanavalin A (Con A)-induced mouse hepatitis model is established for studying liver injury.
- Limited research exists on Con A's impact on organs outside the liver.
Purpose of the Study:
- To investigate the effects of Con A administration on extrahepatic organs, specifically the spleen, kidney, and lung.
- To analyze the expression of cytokine messenger RNA (mRNA) in these organs following Con A treatment.
Main Methods:
- Histopathological examination of liver, spleen, kidney, and lung tissues.
- Messenger RNA (mRNA) expression analysis using polymerase chain reaction (PCR).
- Assessment of cytokine mRNA induction (interleukin-2, interferon-gamma, tumor necrosis factor-alpha) and T-cell marker mRNA (CD4, CD8).
Main Results:
- Con A administration induced histopathological changes in the liver, spleen, kidney, and lung.
- Con A upregulated interleukin-2 mRNA in the spleen and, to a lesser extent, the kidney.
- Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) mRNA were induced in all examined organs; IFN-gamma mRNA induction was inhibited by cyclosporine A, unlike TNF-alpha mRNA.
Conclusions:
- Con A exerts pathological effects not only on the liver but also on extrahepatic organs like the spleen, kidney, and lung.
- Con A induces the expression of pro-inflammatory cytokine mRNAs in these organs, suggesting a systemic inflammatory response.
- The differential inhibition of IFN-gamma mRNA by cyclosporine A suggests distinct pathways for Con A-induced cytokine mRNA expression.