Beta-hydroxy-beta-methylbutyrate Inhibits Lipopolysaccharide-induced Interleukin-6 Expression by Increasing Protein Phosphatase-1α Expression

Mitsutaka Yakabe; Sumito Ogawa; Hidetaka Ota; Katsuya Iijima; Masato Eto; Yasuyoshi Ouchi; Masahiro Akishita

doi:doi:10.11648/j.bs.20150101.11

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Beta-hydroxy-beta-methylbutyrate Inhibits Lipopolysaccharide-induced Interleukin-6 Expression by Increasing Protein Phosphatase-1α Expression

Mitsutaka Yakabe, Sumito Ogawa, Hidetaka Ota, Katsuya Iijima, Masato Eto, Yasuyoshi Ouchi, Masahiro Akishita

Published in Biomedical Sciences (Volume 1, Issue 1)

Received: 15 May 2015 Accepted: 25 May 2015 Published: 26 May 2015

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Abstract

Beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, has been suggested to inhibit inflammation. However, its mechanism is not fully understood. Here we show that HMB repressed LPS-induced interleukin-6 (IL-6) expression by inhibiting the NF-B and AP-1 pathways. When protein phosphatase-1 (PP1) was knocked down, the effects of HMB were partly abrogated. We conclude that HMB might repress inflammation by modulating PP1 and its downstream NF-B and AP-1 pathways.

Published in	Biomedical Sciences (Volume 1, Issue 1)
DOI	10.11648/j.bs.20150101.11
Page(s)	1-5
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2015. Published by Science Publishing Group

Keywords

Interleukin-6 (IL-6), NF-B (Nuclear Factor-B), p38, c-Jun N-terminal Kinase (JNK), Beta-hydroxy-beta-methylbutyrate (HMB)

References

[1]	Zhao Z, Satsu H, Fujisawa M, Hori M, Ishimoto Y, Totsuka M, Nambu A, Kakuta S, Ozaki H, Shimizu M (2008) Attenuation by dietary taurine of dextran sulfate sodium-induced colitis in mice and of THP-1-induced damage to intestinal Caco-2 cell monolayers. Amino Acids 35:217-224.
[2]	Capuozzo E, Pecci L, Conrado AB, Fontana M (2013) Thiotaurine prevents apoptosis of human neutrophils: a putative role in inflammation. Adv Exp Med Biol 775:227-236.
[3]	Nicastro H, da Luz CR, Chaves DF, Bechara LR, Voltarelli VA, Rogero MM, Lancha AH, Jr. (2012) Does Branched-Chain Amino Acids Supplementation Modulate Skeletal Muscle Remodeling through Inflammation Modulation? Possible Mechanisms of Action. J Nutr Metab 2012:136937.
[4]	Eley HL, Russell ST, Tisdale MJ (2007) Effect of branched-chain amino acids on muscle atrophy in cancer cachexia. Biochem J 407:113-120.
[5]	Fitschen PJ, Wilson GJ, Wilson JM, Wilund KR (2013) Efficacy of beta-hydroxy-beta-methylbutyrate supplementation in elderly and clinical populations. Nutrition 29:29-36.
[6]	Aversa Z, Bonetto A, Costelli P, Minero VG, Penna F, Baccino FM, Lucia S, Rossi Fanelli F, Muscaritoli M (2011) beta-hydroxy-beta-methylbutyrate (HMB) attenuates muscle and body weight loss in experimental cancer cachexia. Int J Oncol 38:713-720.
[7]	Aversa Z, Alamdari N, Castillero E, Muscaritoli M, Rossi Fanelli F, Hasselgren PO (2012) beta-Hydroxy-beta-methylbutyrate (HMB) prevents dexamethasone-induced myotube atrophy. Biochem Biophys Res Commun 423:739-743.
[8]	Nunes EA, Lomax AR, Noakes PS, Miles EA, Fernandes LC, Calder PC (2011) beta-Hydroxy-beta-methylbutyrate modifies human peripheral blood mononuclear cell proliferation and cytokine production in vitro. Nutrition 27:92-99.
[9]	Hsieh LC, Chien SL, Huang MS, Tseng HF, Chang CK (2006) Anti-inflammatory and anticatabolic effects of short-term beta-hydroxy-beta-methylbutyrate supplementation on chronic obstructive pulmonary disease patients in intensive care unit. Asia Pac J Clin Nutr 15:544-550.
[10]	Yavas C, Yavas G, Acar H, Toy H, Yuce D, Akyurek S, Ata O (2013) Amelioration of radiation-induced acute inflammation and mucosal atrophy by beta-hydroxy-beta-methylbutyrate, L-glutamine, and L-arginine: results of an experimental study. Support Care Cancer 21:883-888.
[11]	Beutler B (2000) Tlr4: central component of the sole mammalian LPS sensor. Curr Opin Immunol 12:20-26.
[12]	Chen C, Chen YH, Lin WW (1999) Involvement of p38 mitogen-activated protein kinase in lipopolysaccharide-induced iNOS and COX-2 expression in J774 macrophages. Immunology 97:124-129.
[13]	Rupec RA, Poujol D, Grosgeorge J, Carle GF, Livolsi A, Peyron JF, Schmid RM, Baeuerle PA, Messer G (1999) Structural analysis, expression, and chromosomal localization of the mouse ikba gene. Immunogenetics 49:395-403.
[14]	Ip YT ,Davis RJ (1998) Signal transduction by the c-Jun N-terminal kinase (JNK)--from inflammation to development. Curr Opin Cell Biol 10:205-219.
[15]	Tanos T, Marinissen MJ, Leskow FC, Hochbaum D, Martinetto H, Gutkind JS, Coso OA (2005) Phosphorylation of c-Fos by members of the p38 MAPK family. Role in the AP-1 response to UV light. J Biol Chem 280:18842-18852.
[16]	Yang D, Tournier C, Wysk M, Lu HT, Xu J, Davis RJ, Flavell RA (1997) Targeted disruption of the MKK4 gene causes embryonic death, inhibition of c-Jun NH2-terminal kinase activation, and defects in AP-1 transcriptional activity. Proc Natl Acad Sci U S A 94:3004-3009.
[17]	Chang L ,Karin M (2001) Mammalian MAP kinase signalling cascades. Nature 410:37-40.
[18]	Dokter WH, Koopmans SB, Vellenga E (1996) Effects of IL-10 and IL-4 on LPS-induced transcription factors (AP-1, NF-IL6 and NF-kappa B) which are involved in IL-6 regulation. Leukemia 10:1308-1316.
[19]	Chen CY, Peng WH, Tsai KD, Hsu SL (2007) Luteolin suppresses inflammation-associated gene expression by blocking NF-kappaB and AP-1 activation pathway in mouse alveolar macrophages. Life Sci 81:1602-1614.
[20]	Jeon YJ, Han SH, Lee YW, Lee M, Yang KH, Kim HM (2000) Dexamethasone inhibits IL-1 beta gene expression in LPS-stimulated RAW 264.7 cells by blocking NF-kappa B/Rel and AP-1 activation. Immunopharmacology 48:173-183.
[21]	Arend WP ,Dayer JM (1990) Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum 33:305-315.
[22]	Castelo-Branco C ,Soveral I (2014) The immune system and aging: a review. Gynecol Endocrinol 30:16-22.
[23]	Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244-254.
[24]	Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, Yang H, Hild M, Kung C, Wilson C, Myer VE, MacKeigan JP, Porter JA, Wang YK, Cantley LC, Finan PM, Murphy LO (2009) Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136:521-534.
[25]	Eley HL, Russell ST, Baxter JH, Mukerji P, Tisdale MJ (2007) Signaling pathways initiated by beta-hydroxy-beta-methylbutyrate to attenuate the depression of protein synthesis in skeletal muscle in response to cachectic stimuli. Am J Physiol Endocrinol Metab 293:E923-931.
[26]	Nunes EA, Kuczera D, Brito GA, Bonatto SJ, Yamazaki RK, Tanhoffer RA, Mund RC, Kryczyk M, Fernandes LC (2008) Beta-hydroxy-beta-methylbutyrate supplementation reduces tumor growth and tumor cell proliferation ex vivo and prevents cachexia in Walker 256 tumor-bearing rats by modifying nuclear factor-kappaB expression. Nutr Res 28:487-493.
[27]	Russell ST ,Tisdale MJ (2009) Mechanism of attenuation by beta-hydroxy-beta-methylbutyrate of muscle protein degradation induced by lipopolysaccharide. Mol Cell Biochem 330:171-179.
[28]	Tan SL, Tareen SU, Melville MW, Blakely CM, Katze MG (2002) The direct binding of the catalytic subunit of protein phosphatase 1 to the PKR protein kinase is necessary but not sufficient for inactivation and disruption of enzyme dimer formation. J Biol Chem 277:36109-36117.
[29]	Goh KC, deVeer MJ, Williams BR (2000) The protein kinase PKR is required for p38 MAPK activation and the innate immune response to bacterial endotoxin. EMBO J 19:4292-4297.
[30]	Lu H, Wu JY, Kudo T, Ohno T, Graham DY, Yamaoka Y (2005) Regulation of interleukin-6 promoter activation in gastric epithelial cells infected with Helicobacter pylori. Mol Biol Cell 16:4954-4966.

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APA Style

Mitsutaka Yakabe, Sumito Ogawa, Hidetaka Ota, Katsuya Iijima, Masato Eto, et al. (2015). Beta-hydroxy-beta-methylbutyrate Inhibits Lipopolysaccharide-induced Interleukin-6 Expression by Increasing Protein Phosphatase-1α Expression. Biomedical Sciences, 1(1), 1-5. https://doi.org/10.11648/j.bs.20150101.11

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ACS Style

Mitsutaka Yakabe; Sumito Ogawa; Hidetaka Ota; Katsuya Iijima; Masato Eto, et al. Beta-hydroxy-beta-methylbutyrate Inhibits Lipopolysaccharide-induced Interleukin-6 Expression by Increasing Protein Phosphatase-1α Expression. Biomed. Sci. 2015, 1(1), 1-5. doi: 10.11648/j.bs.20150101.11

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AMA Style

Mitsutaka Yakabe, Sumito Ogawa, Hidetaka Ota, Katsuya Iijima, Masato Eto, et al. Beta-hydroxy-beta-methylbutyrate Inhibits Lipopolysaccharide-induced Interleukin-6 Expression by Increasing Protein Phosphatase-1α Expression. Biomed Sci. 2015;1(1):1-5. doi: 10.11648/j.bs.20150101.11

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@article{10.11648/j.bs.20150101.11,
  author = {Mitsutaka Yakabe and Sumito Ogawa and Hidetaka Ota and Katsuya Iijima and Masato Eto and Yasuyoshi Ouchi and Masahiro Akishita},
  title = {Beta-hydroxy-beta-methylbutyrate Inhibits Lipopolysaccharide-induced Interleukin-6 Expression by Increasing Protein Phosphatase-1α Expression},
  journal = {Biomedical Sciences},
  volume = {1},
  number = {1},
  pages = {1-5},
  doi = {10.11648/j.bs.20150101.11},
  url = {https://doi.org/10.11648/j.bs.20150101.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.bs.20150101.11},
  abstract = {Beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, has been suggested to inhibit inflammation. However, its mechanism is not fully understood. Here we show that HMB repressed LPS-induced interleukin-6 (IL-6) expression by inhibiting the NF-B and AP-1 pathways. When protein phosphatase-1 (PP1) was knocked down, the effects of HMB were partly abrogated. We conclude that HMB might repress inflammation by modulating PP1 and its downstream NF-B and AP-1 pathways.},
 year = {2015}
}

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TY  - JOUR
T1  - Beta-hydroxy-beta-methylbutyrate Inhibits Lipopolysaccharide-induced Interleukin-6 Expression by Increasing Protein Phosphatase-1α Expression
AU  - Mitsutaka Yakabe
AU  - Sumito Ogawa
AU  - Hidetaka Ota
AU  - Katsuya Iijima
AU  - Masato Eto
AU  - Yasuyoshi Ouchi
AU  - Masahiro Akishita
Y1  - 2015/05/26
PY  - 2015
N1  - https://doi.org/10.11648/j.bs.20150101.11
DO  - 10.11648/j.bs.20150101.11
T2  - Biomedical Sciences
JF  - Biomedical Sciences
JO  - Biomedical Sciences
SP  - 1
EP  - 5
PB  - Science Publishing Group
SN  - 2575-3932
UR  - https://doi.org/10.11648/j.bs.20150101.11
AB  - Beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, has been suggested to inhibit inflammation. However, its mechanism is not fully understood. Here we show that HMB repressed LPS-induced interleukin-6 (IL-6) expression by inhibiting the NF-B and AP-1 pathways. When protein phosphatase-1 (PP1) was knocked down, the effects of HMB were partly abrogated. We conclude that HMB might repress inflammation by modulating PP1 and its downstream NF-B and AP-1 pathways.
VL  - 1
IS  - 1
ER  -

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Author Information

Mitsutaka Yakabe

Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Sumito Ogawa

Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Hidetaka Ota

Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Katsuya Iijima

Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Masato Eto

Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Yasuyoshi Ouchi

Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Masahiro Akishita

Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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Plain Text BibTeX RIS

APA Style

Mitsutaka Yakabe, Sumito Ogawa, Hidetaka Ota, Katsuya Iijima, Masato Eto, et al. (2015). Beta-hydroxy-beta-methylbutyrate Inhibits Lipopolysaccharide-induced Interleukin-6 Expression by Increasing Protein Phosphatase-1α Expression. Biomedical Sciences, 1(1), 1-5. https://doi.org/10.11648/j.bs.20150101.11

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ACS Style

Mitsutaka Yakabe; Sumito Ogawa; Hidetaka Ota; Katsuya Iijima; Masato Eto, et al. Beta-hydroxy-beta-methylbutyrate Inhibits Lipopolysaccharide-induced Interleukin-6 Expression by Increasing Protein Phosphatase-1α Expression. Biomed. Sci. 2015, 1(1), 1-5. doi: 10.11648/j.bs.20150101.11

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AMA Style

Mitsutaka Yakabe, Sumito Ogawa, Hidetaka Ota, Katsuya Iijima, Masato Eto, et al. Beta-hydroxy-beta-methylbutyrate Inhibits Lipopolysaccharide-induced Interleukin-6 Expression by Increasing Protein Phosphatase-1α Expression. Biomed Sci. 2015;1(1):1-5. doi: 10.11648/j.bs.20150101.11

Copy | Download

@article{10.11648/j.bs.20150101.11,
  author = {Mitsutaka Yakabe and Sumito Ogawa and Hidetaka Ota and Katsuya Iijima and Masato Eto and Yasuyoshi Ouchi and Masahiro Akishita},
  title = {Beta-hydroxy-beta-methylbutyrate Inhibits Lipopolysaccharide-induced Interleukin-6 Expression by Increasing Protein Phosphatase-1α Expression},
  journal = {Biomedical Sciences},
  volume = {1},
  number = {1},
  pages = {1-5},
  doi = {10.11648/j.bs.20150101.11},
  url = {https://doi.org/10.11648/j.bs.20150101.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.bs.20150101.11},
  abstract = {Beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, has been suggested to inhibit inflammation. However, its mechanism is not fully understood. Here we show that HMB repressed LPS-induced interleukin-6 (IL-6) expression by inhibiting the NF-B and AP-1 pathways. When protein phosphatase-1 (PP1) was knocked down, the effects of HMB were partly abrogated. We conclude that HMB might repress inflammation by modulating PP1 and its downstream NF-B and AP-1 pathways.},
 year = {2015}
}

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TY  - JOUR
T1  - Beta-hydroxy-beta-methylbutyrate Inhibits Lipopolysaccharide-induced Interleukin-6 Expression by Increasing Protein Phosphatase-1α Expression
AU  - Mitsutaka Yakabe
AU  - Sumito Ogawa
AU  - Hidetaka Ota
AU  - Katsuya Iijima
AU  - Masato Eto
AU  - Yasuyoshi Ouchi
AU  - Masahiro Akishita
Y1  - 2015/05/26
PY  - 2015
N1  - https://doi.org/10.11648/j.bs.20150101.11
DO  - 10.11648/j.bs.20150101.11
T2  - Biomedical Sciences
JF  - Biomedical Sciences
JO  - Biomedical Sciences
SP  - 1
EP  - 5
PB  - Science Publishing Group
SN  - 2575-3932
UR  - https://doi.org/10.11648/j.bs.20150101.11
AB  - Beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, has been suggested to inhibit inflammation. However, its mechanism is not fully understood. Here we show that HMB repressed LPS-induced interleukin-6 (IL-6) expression by inhibiting the NF-B and AP-1 pathways. When protein phosphatase-1 (PP1) was knocked down, the effects of HMB were partly abrogated. We conclude that HMB might repress inflammation by modulating PP1 and its downstream NF-B and AP-1 pathways.
VL  - 1
IS  - 1
ER  -

Copy | Download