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Bee venom phospholipase A2 protects against acetaminophen-induced acute liver injury by modulating regulatory T cells and IL-10 in mice.

Kim H, Keum DJ, Kwak Jw, Chung HS, Bae H - PLoS ONE (2014)

Bottom Line: We previously found that bee venom strongly increased the Treg population in splenocytes and subsequently suppressed immune disorders.More recently, we found that the effective component of bee venom is PLA2.Based on these findings, it can be concluded that the protective effects of PLA2 against acetaminophen-induced hepatotoxicity can be mediated by modulating the Treg and IL-10 production.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.

ABSTRACT
The aim of this study was to investigate the protective effects of phospholipase A2 (PLA2) from bee venom against acetaminophen-induced hepatotoxicity through CD4+CD25+Foxp3+ T cells (Treg) in mice. Acetaminophen (APAP) is a widely used antipyretic and analgesic, but an acute or cumulative overdose of acetaminophen can cause severe hepatic failure. Tregs have been reported to possess protective effects in various liver diseases and kidney toxicity. We previously found that bee venom strongly increased the Treg population in splenocytes and subsequently suppressed immune disorders. More recently, we found that the effective component of bee venom is PLA2. Thus, we hypothesized that PLA2 could protect against liver injury induced by acetaminophen. To evaluate the hepatoprotective effects of PLA2, C57BL/6 mice or interleukin-10-deficient (IL-10-/-) mice were injected with PLA2 once a day for five days and sacrificed 24 h (h) after acetaminophen injection. The blood sera were collected 0, 6, and 24 h after acetaminophen injection for the analysis of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PLA2-injected mice showed reduced levels of serum AST, ALT, proinflammatory cytokines, and nitric oxide (NO) compared with the PBS-injected control mice. However, IL-10 was significantly increased in the PLA2-injected mice. These hepatic protective effects were abolished in Treg-depleted mice by antibody treatment and in IL-10-/- mice. Based on these findings, it can be concluded that the protective effects of PLA2 against acetaminophen-induced hepatotoxicity can be mediated by modulating the Treg and IL-10 production.

No MeSH data available.


Related in: MedlinePlus

Increase of the Treg population in splenocytes by PLA2.Splenocytes from Foxp3EGFP mice were treated with various concentrations of PLA2 and PBS for three days. The flow cytometry data showed a population of Tregs in the groups of PBS-treated and PLA2 (10 µg/ml)-treated CD4+ T cells (A). The populations of CD25+Foxp3+ T cells treated with various concentrations of PLA2 are depicted as percentages of the total CD4+ T cells (B). The values shown indicate the means ± S.E.M. *P<0.05 vs. PBS, **P<0.01 vs. PBS, ***P<0.01 vs. PBS.
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pone-0114726-g001: Increase of the Treg population in splenocytes by PLA2.Splenocytes from Foxp3EGFP mice were treated with various concentrations of PLA2 and PBS for three days. The flow cytometry data showed a population of Tregs in the groups of PBS-treated and PLA2 (10 µg/ml)-treated CD4+ T cells (A). The populations of CD25+Foxp3+ T cells treated with various concentrations of PLA2 are depicted as percentages of the total CD4+ T cells (B). The values shown indicate the means ± S.E.M. *P<0.05 vs. PBS, **P<0.01 vs. PBS, ***P<0.01 vs. PBS.

Mentions: To evaluate the immune-modulating effect of PLA2 in splenocytes, the splenocytes from Foxp3EGFP mice were treated with PLA2 or PBS for three days. The Treg population was dose-dependently increased in the PLA2-treated group compared with the PBS-treated group (Fig. 1).


Bee venom phospholipase A2 protects against acetaminophen-induced acute liver injury by modulating regulatory T cells and IL-10 in mice.

Kim H, Keum DJ, Kwak Jw, Chung HS, Bae H - PLoS ONE (2014)

Increase of the Treg population in splenocytes by PLA2.Splenocytes from Foxp3EGFP mice were treated with various concentrations of PLA2 and PBS for three days. The flow cytometry data showed a population of Tregs in the groups of PBS-treated and PLA2 (10 µg/ml)-treated CD4+ T cells (A). The populations of CD25+Foxp3+ T cells treated with various concentrations of PLA2 are depicted as percentages of the total CD4+ T cells (B). The values shown indicate the means ± S.E.M. *P<0.05 vs. PBS, **P<0.01 vs. PBS, ***P<0.01 vs. PBS.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257707&req=5

pone-0114726-g001: Increase of the Treg population in splenocytes by PLA2.Splenocytes from Foxp3EGFP mice were treated with various concentrations of PLA2 and PBS for three days. The flow cytometry data showed a population of Tregs in the groups of PBS-treated and PLA2 (10 µg/ml)-treated CD4+ T cells (A). The populations of CD25+Foxp3+ T cells treated with various concentrations of PLA2 are depicted as percentages of the total CD4+ T cells (B). The values shown indicate the means ± S.E.M. *P<0.05 vs. PBS, **P<0.01 vs. PBS, ***P<0.01 vs. PBS.
Mentions: To evaluate the immune-modulating effect of PLA2 in splenocytes, the splenocytes from Foxp3EGFP mice were treated with PLA2 or PBS for three days. The Treg population was dose-dependently increased in the PLA2-treated group compared with the PBS-treated group (Fig. 1).

Bottom Line: We previously found that bee venom strongly increased the Treg population in splenocytes and subsequently suppressed immune disorders.More recently, we found that the effective component of bee venom is PLA2.Based on these findings, it can be concluded that the protective effects of PLA2 against acetaminophen-induced hepatotoxicity can be mediated by modulating the Treg and IL-10 production.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.

ABSTRACT
The aim of this study was to investigate the protective effects of phospholipase A2 (PLA2) from bee venom against acetaminophen-induced hepatotoxicity through CD4+CD25+Foxp3+ T cells (Treg) in mice. Acetaminophen (APAP) is a widely used antipyretic and analgesic, but an acute or cumulative overdose of acetaminophen can cause severe hepatic failure. Tregs have been reported to possess protective effects in various liver diseases and kidney toxicity. We previously found that bee venom strongly increased the Treg population in splenocytes and subsequently suppressed immune disorders. More recently, we found that the effective component of bee venom is PLA2. Thus, we hypothesized that PLA2 could protect against liver injury induced by acetaminophen. To evaluate the hepatoprotective effects of PLA2, C57BL/6 mice or interleukin-10-deficient (IL-10-/-) mice were injected with PLA2 once a day for five days and sacrificed 24 h (h) after acetaminophen injection. The blood sera were collected 0, 6, and 24 h after acetaminophen injection for the analysis of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PLA2-injected mice showed reduced levels of serum AST, ALT, proinflammatory cytokines, and nitric oxide (NO) compared with the PBS-injected control mice. However, IL-10 was significantly increased in the PLA2-injected mice. These hepatic protective effects were abolished in Treg-depleted mice by antibody treatment and in IL-10-/- mice. Based on these findings, it can be concluded that the protective effects of PLA2 against acetaminophen-induced hepatotoxicity can be mediated by modulating the Treg and IL-10 production.

No MeSH data available.


Related in: MedlinePlus