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Role of CpG ODN in concanavalin A-induced hepatitis in mice
Kazumichi Abe1, Hiromasa Ohira, Hiroko Kobayashi
1Department of Internal Medicine II, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan.
Objective:
To investigate the effects of an intradermal injection of oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs on concanavalin A (Con A)-induced hepatitis, an experimental model of immune-mediated hepatitis.
Methods:
Con A was injected intravenously into Balb/c mice. Twelve hours after Con A challenge, blood and liver samples were obtained. CpG ODN was injected intradermally 48 hours before Con A challenge. The extent of liver injury was assessed by determining serum alanine transaminase (ALT) and by liver histology. Serum levels of cytokines, including interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4 and IL-5, were measured by enzyme-linked immunosorbent assay.
Results:
Co-administration of Con A and CpG ODN significantly increased serum ALT in mice compared with that in the case of administration of Con A alone (10,268 +/- 4,654 and 1,140 +/- 832 IU/1, respectively, p<0.05). In liver histology, mice treated with CpG ODN and Con A showed more extensive midzonal necrosis than did mice treated with Con A alone. These mice also showed significant increases in serum TNF-alpha and IFN-gamma and decrease in serum IL-5.
Conclusions:
The results indicate that CpG ODNs aggravate Con A-induced hepatitis by stimulating the production of T-helper-1 (Th1) cytokines, TNF-alpha and IFN-gamma, suggesting that bacterial DNA that contains unmethylated CpG motifs may contribute to the exacerbation of immune-mediated liver injury.
Insights
Oligodeoxynucleotides (ODNs) with CpG motifs worsen concanavalin A (Con A)-induced hepatitis in mice. This immune-mediated liver injury is exacerbated by increased T-helper-1 (Th1) cytokines, suggesting bacterial DNA may worsen liver damage.
Area of Science:
- Immunology
- Hepatology
- Molecular Biology
Background:
- Immune-mediated hepatitis, such as concanavalin A (Con A)-induced hepatitis in mice, serves as a model for studying liver injury.
- Oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs are known immune stimulants.
Purpose of the Study:
- To investigate the impact of intradermal CpG ODN injection on Con A-induced hepatitis.
- To understand the role of CpG ODNs in modulating immune responses during experimental liver injury.
Main Methods:
- Balb/c mice were challenged with Con A intravenously.
- CpG ODN was administered intradermally 48 hours prior to Con A challenge.
- Liver injury was assessed via serum alanine transaminase (ALT) levels and liver histology. Cytokine levels (IFN-gamma, TNF-alpha, IL-4, IL-5) were measured.
Main Results:
- Co-administration of CpG ODN and Con A significantly elevated serum ALT levels compared to Con A alone.
- CpG ODN treatment led to more extensive liver necrosis and increased serum levels of TNF-alpha and IFN-gamma.
- A significant decrease in serum IL-5 was observed in mice treated with both Con A and CpG ODN.
Conclusions:
- CpG ODNs aggravate Con A-induced hepatitis by stimulating T-helper-1 (Th1) cytokine production (TNF-alpha and IFN-gamma).
- These findings suggest that bacterial DNA containing unmethylated CpG motifs may contribute to the exacerbation of immune-mediated liver injury.
