Deficiency of Interleukin-15 Enhances Susceptibility to Acetaminophen-Induced Liver Injury in Mice

Hsein-San Hou; Ching-Len Liao; Huey-Kang Sytwu; Nan-Shih Liao; Tien-Yu Huang; Tsai-Yuan Hsieh; Heng-Cheng Chu

doi:10.1371/journal.pone.0044880

Deficiency of Interleukin-15 Enhances Susceptibility to Acetaminophen-Induced Liver Injury in Mice

Hsein-San Hou, Ching-Len Liao, Huey-Kang Sytwu, Nan-Shih Liao, Tien-Yu Huang, Tsai-Yuan Hsieh, Heng-Cheng Chu

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

Hepatocytes have a direct necrotic role in acetaminophen (APAP)-induced liver injury (AILI), prolonged secondary inflammatory response through innate immune cells and cytokines also significantly contributes to APAP hepatotoxicity. Interleukin 15 (IL-15), a multifunction cytokine, regulates the adaptive immune system and influences development and function of innate immune cells. To better understand the role of IL-15 in liver injury, we treated wild-type (WT) and IL-15-knockout (Il15-/-) mice with a hepatotoxic dose of APAP to induce AILI and evaluated animal survival, liver damage, APAP metabolism in livers and the inflammatory response. Production of pro-inflammatory cytokines/chemokines was greater in Il15-/- than WT mice. Subanalysis of hepatic infiltrated monocytes revealed greater neutrophil influx, along with greater hepatic induction of inducible nitric oxide synthase (iNOS), in Il15-/- than WT mice. In addition, the level of hepatic hemeoxygenase 1 (HO-1) was partially suppressed in Il15-/- mice, but not in WT mice. Interestingly, elimination of Kupffer cells and neutrophils did not alter the vulnerability to excess APAP in Il15-/- mice. However, injection of galactosamine, a hepatic transcription inhibitor, significantly reduced the increased APAP sensitivity in Il15-/- mice but had minor effect on WT mice. We demonstrated that deficiency of IL-15 increased mouse susceptibility to AILI. Moreover, Kupffer cell might affect APAP hepatotoxicity through IL-15. © 2012 Hou et al.

Original language	English
Journal	PLoS One
Volume	7
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0044880
Publication status	Published - 2012
Externally published	Yes

Keywords

galactosamine
gamma interferon
glutathione
heme oxygenase 1
inducible nitric oxide synthase
interleukin 15
interleukin 1beta
paracetamol
recombinant interleukin 15
tumor necrosis factor alpha
animal cell
animal experiment
animal model
animal tissue
article
cell infiltration
cell transport
controlled study
cytokine production
disease predisposition
drug metabolism
knockout mouse
Kupffer cell
liver cell
male
monocyte
mouse
neutrophil
nonhuman
protein blood level
protein deficiency
survival
toxic hepatitis
wild type
Acetaminophen
Animals
Antibodies, Neutralizing
Disease Susceptibility
Dose-Response Relationship, Drug
Drug-Induced Liver Injury
Enzyme Induction
Gene Knockout Techniques
Heme Oxygenase-1
Hepatitis
Interleukin-15
Kupffer Cells
Liver
Male
Mice
Mice, Inbred C57BL
Nitric Oxide Synthase Type II
Organ Specificity
Recombinant Proteins
Transcription, Genetic
Animalia
Mus

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0044880

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Cite this

@article{892ddbdacc4847ca9030305df6f610c3,

title = "Deficiency of Interleukin-15 Enhances Susceptibility to Acetaminophen-Induced Liver Injury in Mice",

abstract = "Hepatocytes have a direct necrotic role in acetaminophen (APAP)-induced liver injury (AILI), prolonged secondary inflammatory response through innate immune cells and cytokines also significantly contributes to APAP hepatotoxicity. Interleukin 15 (IL-15), a multifunction cytokine, regulates the adaptive immune system and influences development and function of innate immune cells. To better understand the role of IL-15 in liver injury, we treated wild-type (WT) and IL-15-knockout (Il15-/-) mice with a hepatotoxic dose of APAP to induce AILI and evaluated animal survival, liver damage, APAP metabolism in livers and the inflammatory response. Production of pro-inflammatory cytokines/chemokines was greater in Il15-/- than WT mice. Subanalysis of hepatic infiltrated monocytes revealed greater neutrophil influx, along with greater hepatic induction of inducible nitric oxide synthase (iNOS), in Il15-/- than WT mice. In addition, the level of hepatic hemeoxygenase 1 (HO-1) was partially suppressed in Il15-/- mice, but not in WT mice. Interestingly, elimination of Kupffer cells and neutrophils did not alter the vulnerability to excess APAP in Il15-/- mice. However, injection of galactosamine, a hepatic transcription inhibitor, significantly reduced the increased APAP sensitivity in Il15-/- mice but had minor effect on WT mice. We demonstrated that deficiency of IL-15 increased mouse susceptibility to AILI. Moreover, Kupffer cell might affect APAP hepatotoxicity through IL-15. {\textcopyright} 2012 Hou et al.",

keywords = "galactosamine, gamma interferon, glutathione, heme oxygenase 1, inducible nitric oxide synthase, interleukin 15, interleukin 1beta, paracetamol, recombinant interleukin 15, tumor necrosis factor alpha, animal cell, animal experiment, animal model, animal tissue, article, cell infiltration, cell transport, controlled study, cytokine production, disease predisposition, drug metabolism, knockout mouse, Kupffer cell, liver cell, male, monocyte, mouse, neutrophil, nonhuman, protein blood level, protein deficiency, survival, toxic hepatitis, wild type, Acetaminophen, Animals, Antibodies, Neutralizing, Disease Susceptibility, Dose-Response Relationship, Drug, Drug-Induced Liver Injury, Enzyme Induction, Gene Knockout Techniques, Heme Oxygenase-1, Hepatitis, Interleukin-15, Kupffer Cells, Liver, Male, Mice, Mice, Inbred C57BL, Nitric Oxide Synthase Type II, Organ Specificity, Recombinant Proteins, Transcription, Genetic, Animalia, Mus",

author = "Hsein-San Hou and Ching-Len Liao and Huey-Kang Sytwu and Nan-Shih Liao and Tien-Yu Huang and Tsai-Yuan Hsieh and Heng-Cheng Chu",

note = "被引用次數：6 Export Date: 22 March 2016 通訊地址: Chu, H.-C.; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 電子郵件： [email protected] 化學物質/CAS: galactosamine, 7535-00-4; gamma interferon, 82115-62-6; glutathione, 70-18-8; inducible nitric oxide synthase, 501433-35-8; paracetamol, 103-90-2; Acetaminophen, 103-90-2; Antibodies, Neutralizing; Heme Oxygenase-1, 1.14.99.3; Interleukin-15; Nitric Oxide Synthase Type II, 1.14.13.39; Recombinant Proteins 參考文獻: Dahlin, D.C., Miwa, G.T., Lu, A.Y., Nelson, S.D., N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen (1984) Proc Natl Acad Sci U S A, 81, pp. 1327-1331; Mitchell, J.R., Jollow, D.J., Potter, W.Z., Gillette, J.R., Brodie, B.B., Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione (1973) J Pharmacol Exp Ther, 187, pp. 211-217; Jaeschke, H., Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo: the protective effect of allopurinol (1990) J Pharmacol Exp Ther, 255, pp. 935-941; Kon, K., Kim, J.S., Jaeschke, H., Lemasters, J.J., Mitochondrial permeability transition in acetaminophen-induced necrosis and apoptosis of cultured mouse hepatocytes (2004) Hepatology, 40, pp. 1170-1179; Chiu, H., Brittingham, J.A., Laskin, D.L., Differential induction of heme oxygenase-1 in macrophages and hepatocytes during acetaminophen-induced hepatotoxicity in the rat: effects of hemin and biliverdin (2002) Toxicol Appl Pharmacol, 181, pp. 106-115; Kaplowitz, N., Idiosyncratic drug hepatotoxicity (2005) Nat Rev Drug Discov, 4, pp. 489-499; Liu, Z.X., Govindarajan, S., Kaplowitz, N., Innate immune system plays a critical role in determining the progression and severity of acetaminophen hepatotoxicity (2004) Gastroenterology, 127, pp. 1760-1774; Liu, Z.X., Han, D., Gunawan, B., Kaplowitz, N., Neutrophil depletion protects against murine acetaminophen hepatotoxicity (2006) Hepatology, 43, pp. 1220-1230; Connolly, M.K., Ayo, D., Malhotra, A., Hackman, M., Bedrosian, A.S., Dendritic cell depletion exacerbates acetaminophen hepatotoxicity (2011) Hepatology, 54, pp. 959-968; Michael, S.L., Pumford, N.R., Mayeux, P.R., Niesman, M.R., Hinson, J.A., Pretreatment of mice with macrophage inactivators decreases acetaminophen hepatotoxicity and the formation of reactive oxygen and nitrogen species (1999) Hepatology, 30, pp. 186-195; Ju, C., Reilly, T.P., Bourdi, M., Radonovich, M.F., Brady, J.N., Protective role of Kupffer cells in acetaminophen-induced hepatic injury in mice (2002) Chem Res Toxicol, 15, pp. 1504-1513; Masson, M.J., Carpenter, L.D., Graf, M.L., Pohl, L.R., Pathogenic role of natural killer T and natural killer cells in acetaminophen-induced liver injury in mice is dependent on the presence of dimethyl sulfoxide (2008) Hepatology, 48, pp. 889-897; Cover, C., Liu, J., Farhood, A., Malle, E., Waalkes, M.P., Pathophysiological role of the acute inflammatory response during acetaminophen hepatotoxicity (2006) Toxicol Appl Pharmacol, 216, pp. 98-107; Bourdi, M., Masubuchi, Y., Reilly, T.P., Amouzadeh, H.R., Martin, J.L., Protection against acetaminophen-induced liver injury and lethality by interleukin 10: role of inducible nitric oxide synthase (2002) Hepatology, 35, pp. 289-298; Masubuchi, Y., Bourdi, M., Reilly, T.P., Graf, M.L., George, J.W., Role of interleukin-6 in hepatic heat shock protein expression and protection against acetaminophen-induced liver disease (2003) Biochem Biophys Res Commun, 304, pp. 207-212; Yee, S.B., Bourdi, M., Masson, M.J., Pohl, L.R., Hepatoprotective role of endogenous interleukin-13 in a murine model of acetaminophen-induced liver disease (2007) Chem Res Toxicol, 20, pp. 734-744; Blazka, M.E., Wilmer, J.L., Holladay, S.D., Wilson, R.E., Luster, M.I., Role of proinflammatory cytokines in acetaminophen hepatotoxicity (1995) Toxicol Appl Pharmacol, 133, pp. 43-52; Ishida, Y., Kondo, T., Ohshima, T., Fujiwara, H., Iwakura, Y., A pivotal involvement of IFN-gamma in the pathogenesis of acetaminophen-induced acute liver injury (2002) FASEB J, 16, pp. 1227-1236; Imaeda, A.B., Watanabe, A., Sohail, M.A., Mahmood, S., Mohamadnejad, M., Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome (2009) J Clin Invest, 119, pp. 305-314; Budagian, V., Bulanova, E., Paus, R., Bulfone-Paus, S., IL-15/IL-15 receptor biology: a guided tour through an expanding universe (2006) Cytokine Growth Factor Rev, 17, pp. 259-280; Ma, A., Koka, R., Burkett, P., Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis (2006) Annu Rev Immunol, 24, pp. 657-679; Ohteki, T., Suzue, K., Maki, C., Ota, T., Koyasu, S., Critical role of IL-15-IL-15R for antigen-presenting cell functions in the innate immune response (2001) Nat Immunol, 2, pp. 1138-1143; Bouchard, A., Ratthe, C., Girard, D., Interleukin-15 delays human neutrophil apoptosis by intracellular events and not via extracellular factors: role of Mcl-1 and decreased activity of caspase-3 and caspase-8 (2004) J Leukoc Biol, 75, pp. 893-900; Alleva, D.G., Kaser, S.B., Monroy, M.A., Fenton, M.J., Beller, D.I., IL-15 functions as a potent autocrine regulator of macrophage proinflammatory cytokine production: evidence for differential receptor subunit utilization associated with stimulation or inhibition (1997) J Immunol, 159, pp. 2941-2951; Li, B., Sun, R., Wei, H., Gao, B., Tian, Z., Interleukin-15 prevents concanavalin A-induced liver injury in mice via NKT cell-dependent mechanism (2006) Hepatology, 43, pp. 1211-1219; Bulfone-Paus, S., Ungureanu, D., Pohl, T., Lindner, G., Paus, R., Interleukin-15 protects from lethal apoptosis in vivo (1997) Nat Med, 3, pp. 1124-1128; Ohteki, T., Tada, H., Ishida, K., Sato, T., Maki, C., Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo (2006) J Exp Med, 203, pp. 2329-2338; Kuwajima, S., Sato, T., Ishida, K., Tada, H., Tezuka, H., Interleukin 15-dependent crosstalk between conventional and plasmacytoid dendritic cells is essential for CpG-induced immune activation (2006) Nat Immunol, 7, pp. 740-746; 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year = "2012",

doi = "10.1371/journal.pone.0044880",

language = "English",

volume = "7",

journal = "PLoS One",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "9",

}

TY - JOUR

T1 - Deficiency of Interleukin-15 Enhances Susceptibility to Acetaminophen-Induced Liver Injury in Mice

AU - Hou, Hsein-San

AU - Liao, Ching-Len

AU - Sytwu, Huey-Kang

AU - Liao, Nan-Shih

AU - Huang, Tien-Yu

AU - Hsieh, Tsai-Yuan

AU - Chu, Heng-Cheng

N1 - 被引用次數：6 Export Date: 22 March 2016 通訊地址: Chu, H.-C.; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 電子郵件： [email protected] 化學物質/CAS: galactosamine, 7535-00-4; gamma interferon, 82115-62-6; glutathione, 70-18-8; inducible nitric oxide synthase, 501433-35-8; paracetamol, 103-90-2; Acetaminophen, 103-90-2; Antibodies, Neutralizing; Heme Oxygenase-1, 1.14.99.3; Interleukin-15; Nitric Oxide Synthase Type II, 1.14.13.39; Recombinant Proteins 參考文獻: Dahlin, D.C., Miwa, G.T., Lu, A.Y., Nelson, S.D., N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen (1984) Proc Natl Acad Sci U S A, 81, pp. 1327-1331; Mitchell, J.R., Jollow, D.J., Potter, W.Z., Gillette, J.R., Brodie, B.B., Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione (1973) J Pharmacol Exp Ther, 187, pp. 211-217; Jaeschke, H., Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo: the protective effect of allopurinol (1990) J Pharmacol Exp Ther, 255, pp. 935-941; Kon, K., Kim, J.S., Jaeschke, H., Lemasters, J.J., Mitochondrial permeability transition in acetaminophen-induced necrosis and apoptosis of cultured mouse hepatocytes (2004) Hepatology, 40, pp. 1170-1179; Chiu, H., Brittingham, J.A., Laskin, D.L., Differential induction of heme oxygenase-1 in macrophages and hepatocytes during acetaminophen-induced hepatotoxicity in the rat: effects of hemin and biliverdin (2002) Toxicol Appl Pharmacol, 181, pp. 106-115; Kaplowitz, N., Idiosyncratic drug hepatotoxicity (2005) Nat Rev Drug Discov, 4, pp. 489-499; Liu, Z.X., Govindarajan, S., Kaplowitz, N., Innate immune system plays a critical role in determining the progression and severity of acetaminophen hepatotoxicity (2004) Gastroenterology, 127, pp. 1760-1774; Liu, Z.X., Han, D., Gunawan, B., Kaplowitz, N., Neutrophil depletion protects against murine acetaminophen hepatotoxicity (2006) Hepatology, 43, pp. 1220-1230; Connolly, M.K., Ayo, D., Malhotra, A., Hackman, M., Bedrosian, A.S., Dendritic cell depletion exacerbates acetaminophen hepatotoxicity (2011) Hepatology, 54, pp. 959-968; Michael, S.L., Pumford, N.R., Mayeux, P.R., Niesman, M.R., Hinson, J.A., Pretreatment of mice with macrophage inactivators decreases acetaminophen hepatotoxicity and the formation of reactive oxygen and nitrogen species (1999) Hepatology, 30, pp. 186-195; Ju, C., Reilly, T.P., Bourdi, M., Radonovich, M.F., Brady, J.N., Protective role of Kupffer cells in acetaminophen-induced hepatic injury in mice (2002) Chem Res Toxicol, 15, pp. 1504-1513; Masson, M.J., Carpenter, L.D., Graf, M.L., Pohl, L.R., Pathogenic role of natural killer T and natural killer cells in acetaminophen-induced liver injury in mice is dependent on the presence of dimethyl sulfoxide (2008) Hepatology, 48, pp. 889-897; Cover, C., Liu, J., Farhood, A., Malle, E., Waalkes, M.P., Pathophysiological role of the acute inflammatory response during acetaminophen hepatotoxicity (2006) Toxicol Appl Pharmacol, 216, pp. 98-107; Bourdi, M., Masubuchi, Y., Reilly, T.P., Amouzadeh, H.R., Martin, J.L., Protection against acetaminophen-induced liver injury and lethality by interleukin 10: role of inducible nitric oxide synthase (2002) Hepatology, 35, pp. 289-298; Masubuchi, Y., Bourdi, M., Reilly, T.P., Graf, M.L., George, J.W., Role of interleukin-6 in hepatic heat shock protein expression and protection against acetaminophen-induced liver disease (2003) Biochem Biophys Res Commun, 304, pp. 207-212; Yee, S.B., Bourdi, M., Masson, M.J., Pohl, L.R., Hepatoprotective role of endogenous interleukin-13 in a murine model of acetaminophen-induced liver disease (2007) Chem Res Toxicol, 20, pp. 734-744; Blazka, M.E., Wilmer, J.L., Holladay, S.D., Wilson, R.E., Luster, M.I., Role of proinflammatory cytokines in acetaminophen hepatotoxicity (1995) Toxicol Appl Pharmacol, 133, pp. 43-52; Ishida, Y., Kondo, T., Ohshima, T., Fujiwara, H., Iwakura, Y., A pivotal involvement of IFN-gamma in the pathogenesis of acetaminophen-induced acute liver injury (2002) FASEB J, 16, pp. 1227-1236; Imaeda, A.B., Watanabe, A., Sohail, M.A., Mahmood, S., Mohamadnejad, M., Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome (2009) J Clin Invest, 119, pp. 305-314; Budagian, V., Bulanova, E., Paus, R., Bulfone-Paus, S., IL-15/IL-15 receptor biology: a guided tour through an expanding universe (2006) Cytokine Growth Factor Rev, 17, pp. 259-280; Ma, A., Koka, R., Burkett, P., Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis (2006) Annu Rev Immunol, 24, pp. 657-679; Ohteki, T., Suzue, K., Maki, C., Ota, T., Koyasu, S., Critical role of IL-15-IL-15R for antigen-presenting cell functions in the innate immune response (2001) Nat Immunol, 2, pp. 1138-1143; Bouchard, A., Ratthe, C., Girard, D., Interleukin-15 delays human neutrophil apoptosis by intracellular events and not via extracellular factors: role of Mcl-1 and decreased activity of caspase-3 and caspase-8 (2004) J Leukoc Biol, 75, pp. 893-900; Alleva, D.G., Kaser, S.B., Monroy, M.A., Fenton, M.J., Beller, D.I., IL-15 functions as a potent autocrine regulator of macrophage proinflammatory cytokine production: evidence for differential receptor subunit utilization associated with stimulation or inhibition (1997) J Immunol, 159, pp. 2941-2951; Li, B., Sun, R., Wei, H., Gao, B., Tian, Z., Interleukin-15 prevents concanavalin A-induced liver injury in mice via NKT cell-dependent mechanism (2006) Hepatology, 43, pp. 1211-1219; Bulfone-Paus, S., Ungureanu, D., Pohl, T., Lindner, G., Paus, R., Interleukin-15 protects from lethal apoptosis in vivo (1997) Nat Med, 3, pp. 1124-1128; Ohteki, T., Tada, H., Ishida, K., Sato, T., Maki, C., Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo (2006) J Exp Med, 203, pp. 2329-2338; Kuwajima, S., Sato, T., Ishida, K., Tada, H., Tezuka, H., Interleukin 15-dependent crosstalk between conventional and plasmacytoid dendritic cells is essential for CpG-induced immune activation (2006) Nat Immunol, 7, pp. 740-746; 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PY - 2012

Y1 - 2012

N2 - Hepatocytes have a direct necrotic role in acetaminophen (APAP)-induced liver injury (AILI), prolonged secondary inflammatory response through innate immune cells and cytokines also significantly contributes to APAP hepatotoxicity. Interleukin 15 (IL-15), a multifunction cytokine, regulates the adaptive immune system and influences development and function of innate immune cells. To better understand the role of IL-15 in liver injury, we treated wild-type (WT) and IL-15-knockout (Il15-/-) mice with a hepatotoxic dose of APAP to induce AILI and evaluated animal survival, liver damage, APAP metabolism in livers and the inflammatory response. Production of pro-inflammatory cytokines/chemokines was greater in Il15-/- than WT mice. Subanalysis of hepatic infiltrated monocytes revealed greater neutrophil influx, along with greater hepatic induction of inducible nitric oxide synthase (iNOS), in Il15-/- than WT mice. In addition, the level of hepatic hemeoxygenase 1 (HO-1) was partially suppressed in Il15-/- mice, but not in WT mice. Interestingly, elimination of Kupffer cells and neutrophils did not alter the vulnerability to excess APAP in Il15-/- mice. However, injection of galactosamine, a hepatic transcription inhibitor, significantly reduced the increased APAP sensitivity in Il15-/- mice but had minor effect on WT mice. We demonstrated that deficiency of IL-15 increased mouse susceptibility to AILI. Moreover, Kupffer cell might affect APAP hepatotoxicity through IL-15. © 2012 Hou et al.

AB - Hepatocytes have a direct necrotic role in acetaminophen (APAP)-induced liver injury (AILI), prolonged secondary inflammatory response through innate immune cells and cytokines also significantly contributes to APAP hepatotoxicity. Interleukin 15 (IL-15), a multifunction cytokine, regulates the adaptive immune system and influences development and function of innate immune cells. To better understand the role of IL-15 in liver injury, we treated wild-type (WT) and IL-15-knockout (Il15-/-) mice with a hepatotoxic dose of APAP to induce AILI and evaluated animal survival, liver damage, APAP metabolism in livers and the inflammatory response. Production of pro-inflammatory cytokines/chemokines was greater in Il15-/- than WT mice. Subanalysis of hepatic infiltrated monocytes revealed greater neutrophil influx, along with greater hepatic induction of inducible nitric oxide synthase (iNOS), in Il15-/- than WT mice. In addition, the level of hepatic hemeoxygenase 1 (HO-1) was partially suppressed in Il15-/- mice, but not in WT mice. Interestingly, elimination of Kupffer cells and neutrophils did not alter the vulnerability to excess APAP in Il15-/- mice. However, injection of galactosamine, a hepatic transcription inhibitor, significantly reduced the increased APAP sensitivity in Il15-/- mice but had minor effect on WT mice. We demonstrated that deficiency of IL-15 increased mouse susceptibility to AILI. Moreover, Kupffer cell might affect APAP hepatotoxicity through IL-15. © 2012 Hou et al.

KW - galactosamine

KW - gamma interferon

KW - glutathione

KW - heme oxygenase 1

KW - inducible nitric oxide synthase

KW - interleukin 15

KW - interleukin 1beta

KW - paracetamol

KW - recombinant interleukin 15

KW - tumor necrosis factor alpha

KW - animal cell

KW - animal experiment

KW - animal model

KW - animal tissue

KW - article

KW - cell infiltration

KW - cell transport

KW - controlled study

KW - cytokine production

KW - disease predisposition

KW - drug metabolism

KW - knockout mouse

KW - Kupffer cell

KW - liver cell

KW - male

KW - monocyte

KW - mouse

KW - neutrophil

KW - nonhuman

KW - protein blood level

KW - protein deficiency

KW - survival

KW - toxic hepatitis

KW - wild type

KW - Acetaminophen

KW - Animals

KW - Antibodies, Neutralizing

KW - Disease Susceptibility

KW - Dose-Response Relationship, Drug

KW - Drug-Induced Liver Injury

KW - Enzyme Induction

KW - Gene Knockout Techniques

KW - Heme Oxygenase-1

KW - Hepatitis

KW - Interleukin-15

KW - Kupffer Cells

KW - Liver

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Nitric Oxide Synthase Type II

KW - Organ Specificity

KW - Recombinant Proteins

KW - Transcription, Genetic

KW - Animalia

KW - Mus

U2 - 10.1371/journal.pone.0044880

DO - 10.1371/journal.pone.0044880

M3 - Article

SN - 1932-6203

VL - 7

JO - PLoS One

JF - PLoS One

IS - 9

ER -

Deficiency of Interleukin-15 Enhances Susceptibility to Acetaminophen-Induced Liver Injury in Mice

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