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NKP30-B7-H6 Interaction Aggravates Hepatocyte Damage through Up-Regulation of Interleukin-32 Expression in Hepatitis B Virus-Related Acute-On-Chronic Liver Failure.

Zou Y, Bao J, Pan X, Lu Y, Liao S, Wang X, Wang G, Lin D - PLoS ONE (2015)

Bottom Line: The effect of IL-32 on the apoptosis of Huh7 cells was evaluated using Annexin V/PI staining analysis.An enhancement of hepatic B7-H6 and IL-32 expression was associated with the severity of liver injury in HBV-ACLF.IL-32 can induce the apoptosis of Huh7 cells in a dose-dependent manner.

View Article: PubMed Central - PubMed

Affiliation: Department of Blood Transfusion, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

ABSTRACT

Background and aims: Previous work conducted by our group has shown that the accumulation of hepatic natural killer (NK) cells and the up-regulation of natural cytotoxicity receptors (NKP30 and NKP46) on NK cells from patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) were correlated with disease progression in HBV-ACLF. The natural cytotoxicity receptors expressed on NK cells are believed to be probable candidates involved in the NK cell-mediated hepatocyte damage in HBV-ACLF. However, the underlying mechanisms remain to be elucidated. In the present study, we aimed to discover the role of NKP30-B7-H6 interaction in NK cells-mediated hepatocyte damage in HBV-ACLF.

Methods: Hepatic expressions of B7-H6 and interleukin-32 (IL-32) were examined by immunochemistry staining in samples from patients with HBV-ACLF or mild chronic hepatitis B (CHB). The cytotoxicity of NK-92 cell against target cells (Huh-7 and LO2) was evaluated by CCK8 assay. Expression of IL-32 in liver NK cell, T cells and NK-92 cell line was detected by the flow cytometric analysis. The effect of IL-32 on the apoptosis of Huh7 cells was evaluated using Annexin V/PI staining analysis.

Results: An enhancement of hepatic B7-H6 and IL-32 expression was associated with the severity of liver injury in HBV-ACLF. And there was a positive association between hepatic B7-H6 and IL-32 expression. Expressions of IL-32 in liver NK cells and T cells were increased in HBV-ACLF patients. In vitro NK-92 cells are highly capable of killing the high B7-H6 expressing Huh7 cells and B7-H6-tansfected hepatocyte line LO2 cells dependent on NKP30 and B7-H6 interaction. Furthermore, NK-92 cells exhibited elevated IL-32 expression when stimulated with anti-NKP30 antibodies or when co-cultured with Huh7 cells. IL-32 can induce the apoptosis of Huh7 cells in a dose-dependent manner.

Conclusion: Our results suggest that NKP30-B7-H6 interaction can aggravate hepatocyte damage, probably through up-regulation of IL-32 expression in HBV-ACLF.

No MeSH data available.


Related in: MedlinePlus

Hepatic B7-H6 expression was positively correlated with liver injury severity in HBV-ACLF patients.The relative mean density of hepatic B7-H6 staining was positively correlated with serum TBIL level in HBV-ALCF patients, with a correlation index of 0.659 (P < 0.05) (Fig 2C). The relative mean density of hepatic B7-H6 staining did not correlate with ALT, AST, or HBV levels (P > 0.05) (Fig 2, A, B and D).
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pone.0134568.g002: Hepatic B7-H6 expression was positively correlated with liver injury severity in HBV-ACLF patients.The relative mean density of hepatic B7-H6 staining was positively correlated with serum TBIL level in HBV-ALCF patients, with a correlation index of 0.659 (P < 0.05) (Fig 2C). The relative mean density of hepatic B7-H6 staining did not correlate with ALT, AST, or HBV levels (P > 0.05) (Fig 2, A, B and D).

Mentions: The relative mean density of hepatic B7-H6 staining was positively correlated with liver injury severity, as evaluated by total bilirubin (TBIL) level, in HBV-ACLF patients (Fig 2C, P < 0.05), with a correlation index of 0.659. However, there was no correlation between hepatic B7-H6 staining density and alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis B virus DNA (HBV-DNA) levels (Fig 2A, 2B and 2D, P > 0.05). These results suggested that NKP30-B7H6 recognition may be involved in NK cell-mediated hepatocyte damage.


NKP30-B7-H6 Interaction Aggravates Hepatocyte Damage through Up-Regulation of Interleukin-32 Expression in Hepatitis B Virus-Related Acute-On-Chronic Liver Failure.

Zou Y, Bao J, Pan X, Lu Y, Liao S, Wang X, Wang G, Lin D - PLoS ONE (2015)

Hepatic B7-H6 expression was positively correlated with liver injury severity in HBV-ACLF patients.The relative mean density of hepatic B7-H6 staining was positively correlated with serum TBIL level in HBV-ALCF patients, with a correlation index of 0.659 (P < 0.05) (Fig 2C). The relative mean density of hepatic B7-H6 staining did not correlate with ALT, AST, or HBV levels (P > 0.05) (Fig 2, A, B and D).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524618&req=5

pone.0134568.g002: Hepatic B7-H6 expression was positively correlated with liver injury severity in HBV-ACLF patients.The relative mean density of hepatic B7-H6 staining was positively correlated with serum TBIL level in HBV-ALCF patients, with a correlation index of 0.659 (P < 0.05) (Fig 2C). The relative mean density of hepatic B7-H6 staining did not correlate with ALT, AST, or HBV levels (P > 0.05) (Fig 2, A, B and D).
Mentions: The relative mean density of hepatic B7-H6 staining was positively correlated with liver injury severity, as evaluated by total bilirubin (TBIL) level, in HBV-ACLF patients (Fig 2C, P < 0.05), with a correlation index of 0.659. However, there was no correlation between hepatic B7-H6 staining density and alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis B virus DNA (HBV-DNA) levels (Fig 2A, 2B and 2D, P > 0.05). These results suggested that NKP30-B7H6 recognition may be involved in NK cell-mediated hepatocyte damage.

Bottom Line: The effect of IL-32 on the apoptosis of Huh7 cells was evaluated using Annexin V/PI staining analysis.An enhancement of hepatic B7-H6 and IL-32 expression was associated with the severity of liver injury in HBV-ACLF.IL-32 can induce the apoptosis of Huh7 cells in a dose-dependent manner.

View Article: PubMed Central - PubMed

Affiliation: Department of Blood Transfusion, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

ABSTRACT

Background and aims: Previous work conducted by our group has shown that the accumulation of hepatic natural killer (NK) cells and the up-regulation of natural cytotoxicity receptors (NKP30 and NKP46) on NK cells from patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) were correlated with disease progression in HBV-ACLF. The natural cytotoxicity receptors expressed on NK cells are believed to be probable candidates involved in the NK cell-mediated hepatocyte damage in HBV-ACLF. However, the underlying mechanisms remain to be elucidated. In the present study, we aimed to discover the role of NKP30-B7-H6 interaction in NK cells-mediated hepatocyte damage in HBV-ACLF.

Methods: Hepatic expressions of B7-H6 and interleukin-32 (IL-32) were examined by immunochemistry staining in samples from patients with HBV-ACLF or mild chronic hepatitis B (CHB). The cytotoxicity of NK-92 cell against target cells (Huh-7 and LO2) was evaluated by CCK8 assay. Expression of IL-32 in liver NK cell, T cells and NK-92 cell line was detected by the flow cytometric analysis. The effect of IL-32 on the apoptosis of Huh7 cells was evaluated using Annexin V/PI staining analysis.

Results: An enhancement of hepatic B7-H6 and IL-32 expression was associated with the severity of liver injury in HBV-ACLF. And there was a positive association between hepatic B7-H6 and IL-32 expression. Expressions of IL-32 in liver NK cells and T cells were increased in HBV-ACLF patients. In vitro NK-92 cells are highly capable of killing the high B7-H6 expressing Huh7 cells and B7-H6-tansfected hepatocyte line LO2 cells dependent on NKP30 and B7-H6 interaction. Furthermore, NK-92 cells exhibited elevated IL-32 expression when stimulated with anti-NKP30 antibodies or when co-cultured with Huh7 cells. IL-32 can induce the apoptosis of Huh7 cells in a dose-dependent manner.

Conclusion: Our results suggest that NKP30-B7-H6 interaction can aggravate hepatocyte damage, probably through up-regulation of IL-32 expression in HBV-ACLF.

No MeSH data available.


Related in: MedlinePlus