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Activation of J774.1 murine macrophages by lactate dehydrogenase

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Abstract

We have already reported that lactate dehydrogenase (LDH) activates lymphocytes in vitro and in vivo. In this paper, we report the activating effects of LDH on the macrophage-like cell line J774.1. LDH was found to enhance production of IL-6 and TNF-α by J774.1 cells in a dose-dependent manner. Transcription levels of IL-6 and TNF-α in J774.1 cells were also enhanced by supplementation with LDH. From immunoblot analysis, it was revealed that LDH enhances the phosphorylation level of JNK in J774.1 cells. Moreover, the JNK inhibitor SP600125 decreased production of IL-6 and TNF-α induced by LDH. NF-κB translocation to the nucleus was also facilitated by LDH. These results was revealed that LDH enhances production of IL-6 and TNF-α by J774.1 cells via the increase of JNK phosphorylation and NF-κB translocation to the nucleus. Our data indicated that macrophages may be activated by LDH released from damaged tissues and cells in our body.

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Abbreviations

AP-1:

Activator protein-1

ELISA:

Enzyme-linked immunosorbent assay

FBS:

Fetal bovine serum

HRP:

Horseradish peroxidase

Ig:

Immunoglobulin

IκB:

Inhibitor of NF-κB

IL:

Interleukin

JNK:

C-Jun NH2-terminal kinase

LDH:

Lactate dehydrogenase

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

NaPB:

Sodium phosphate buffer

NF-κB:

Nuclear factor-κB

SD:

Standard derivation

TBS-T:

Tris-buffered saline with 0.1 % Tween 20

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

References

  • Daifuku M, Nishi K, Okamoto T, Nakano H, Nishimoto S, Sugahara T (2012a) Immunostimulatory effects of water extract from Bulbus arteriosus in tuna in vitro. J Funct Foods 4:263–270

    Article  CAS  Google Scholar 

  • Daifuku M, Nishi K, Okamoto T, Nishimoto S, Sugahara T (2012b) Immunomodulatory effects of lactate dehydrogenase in vitro and in vivo. J Funct Foods 4:972–978

    Article  CAS  Google Scholar 

  • Hommes DW, Peppelenbosch MP, Van Deventer SJ (2003) Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut 52:144–151

    Article  CAS  Google Scholar 

  • Lu YC, Yeh WC, Ohashi PS (2008) LPS/TLR4 signal transduction pathway. Cytokine 42:145–151

    Article  CAS  Google Scholar 

  • Masuda Y, Kodama N, Nanba H (2006) Macrophage J774.1 cell is activated by MZ-Fraction (Klasma-MZ) polysaccharide in Grifola frondosa. Mycoscience 47:360–366

    Article  CAS  Google Scholar 

  • Murray PJ, Wynn TA (2011) Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 11:723–737

    Article  CAS  Google Scholar 

  • Nishikori M (2005) Classical and alternative NF-κB activation pathways and their roles in lymphoid malignancies. J Clin Exp Hematopathol 45:15–24

    Article  Google Scholar 

  • Nworu CS, Akah PA, Okoye FB, Proksch P, Esimone CO (2010) The effects of Phyllanthus niruri aqueous extract on the activation of murine lymphocytes and bone marrow-derived macrophages. Immunol Invest 39:245–267

    Article  CAS  Google Scholar 

  • Putra ABN, Morishige H, Nishimoto S, Nishi K, Shiraishi R, Doi M, Sugahara T (2012) Effect of collagens from jellyfish and bovine Achilles’ tendon on the activity of J774.1 and mouse peritoneal macrophage cells. J Funct Foods 4:504–512

    Article  CAS  Google Scholar 

  • Qin Q, Niu J, Wang Z, Xu W, Qiao Z, Gu Y (2012) Astragalus embranaceus extract activates immune response in macrophages via heparanase. Molecules 17:7232–7240

    Article  CAS  Google Scholar 

  • Sugahara T, Shimizu S, Abiru M, Matsuoka S, Sasaki T (1998) A novel function of enolase from rabbit muscle; an immunoglobulin production stimulating factor. Biochim Biophys Acta 1380:163–176

    Article  CAS  Google Scholar 

  • Sullivan AM, Laba JG, Moore JA, Lee TD (2008) Echinacea-induced macrophage activation. Immunopharmacol Immunotoxicol 30:553–574

    Article  CAS  Google Scholar 

  • Takenouchi S, Sugahara T (2002) Lactate dehydrogenase enhances immunoglobulin production by human hybridoma and human peripheral blood lymphocytes. Cytotechnology 42:133–143

    Article  Google Scholar 

  • Tsuji S, Qureshi MA, Hou EW, Fitch WM, Li SS (1994) Evolutionary relationships of lactate dehydrogenases (LDHs) from mammals, birds, an amphibian, fish, barley, and bacteria: LDH cDNA sequences from Xenopus, pig, and rat. Proc Natl Acad Sci USA 91:9392–9396

    Article  CAS  Google Scholar 

  • Turpaev KT (2006) Role of transcription factor AP-1 in integration of cellular signaling systems. Mol Biol 40:945–961

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Faculty of Agriculture, Ehime University, Matsuyama, Ehime, 790-8566, Japan

    Miho Daifuku, Kosuke Nishi & Takuya Sugahara

  2. Faculty of Education, Ehime University, Matsuyama, Ehime, 790-8577, Japan

    Takeaki Okamoto

  3. South Ehime Fisheries Research Center, Ehime University, Ainan, Ehime, 798-4292, Japan

    Takuya Sugahara

  4. Food and Health Sciences Research Center, Ehime University, Matsuyama, Ehime, 790-8566, Japan

    Takuya Sugahara

Authors
  1. Miho Daifuku
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  2. Kosuke Nishi
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  3. Takeaki Okamoto
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  4. Takuya Sugahara
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Correspondence to Takuya Sugahara.

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Daifuku, M., Nishi, K., Okamoto, T. et al. Activation of J774.1 murine macrophages by lactate dehydrogenase. Cytotechnology 66, 937–943 (2014). https://doi.org/10.1007/s10616-013-9646-3

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  • DOI: https://doi.org/10.1007/s10616-013-9646-3

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