Inhibition of lactate dehydrogenase A suppresses inflammatory response in RAW 264.7 macrophages

  • Authors:
    • Yoo‑Jeong Song
    • Ahyeon Kim
    • Goon‑Tae Kim
    • Han Young Yu
    • Eun‑So Lee
    • Mi Jin Park
    • Young‑Jun Kim
    • Soon‑Mi Shim
    • Tae‑Sik Park
  • View Affiliations

  • Published online on: November 20, 2018     https://doi.org/10.3892/mmr.2018.9678
  • Pages: 629-637
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Abstract

Lactate is an important metabolite in cellular metabolism and fluctuates in certain disease conditions including cancer and immune diseases. It was hypothesized that a decrease in lactate would modulate the inflammatory response elicited by lipopolysaccharides (LPS) in macrophages. When RAW 264.7 macrophages were treated with FX11, a specific lactate dehydrogenase (LDHA) inhibitor, the expression of the cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX‑2) was downregulated due to reduced cellular lactate levels. Genetic suppression of LDHA by small interfering RNA (siRNA) downregulated the LPS‑activated expression of interleukin (IL)‑6, iNOS, and COX‑2, and reduced the production of IL‑6 and nitrites. Pharmacological and genetic suppression of LDHA inhibited the phosphorylation of p38 mitogen‑activated protein kinase. Microarray gene expression profile demonstrated that the genes involved in cell proliferation and inflammation were mainly altered by siRNA‑mediated LDHA suppression. Collectively, the present observations suggest that lactate may be an important metabolite and implicated in regulation of inflammatory response.
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January-2019
Volume 19 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Song YJ, Kim A, Kim GT, Yu HY, Lee ES, Park MJ, Kim YJ, Shim SM and Park TS: Inhibition of lactate dehydrogenase A suppresses inflammatory response in RAW 264.7 macrophages. Mol Med Rep 19: 629-637, 2019
APA
Song, Y., Kim, A., Kim, G., Yu, H.Y., Lee, E., Park, M.J. ... Park, T. (2019). Inhibition of lactate dehydrogenase A suppresses inflammatory response in RAW 264.7 macrophages. Molecular Medicine Reports, 19, 629-637. https://doi.org/10.3892/mmr.2018.9678
MLA
Song, Y., Kim, A., Kim, G., Yu, H. Y., Lee, E., Park, M. J., Kim, Y., Shim, S., Park, T."Inhibition of lactate dehydrogenase A suppresses inflammatory response in RAW 264.7 macrophages". Molecular Medicine Reports 19.1 (2019): 629-637.
Chicago
Song, Y., Kim, A., Kim, G., Yu, H. Y., Lee, E., Park, M. J., Kim, Y., Shim, S., Park, T."Inhibition of lactate dehydrogenase A suppresses inflammatory response in RAW 264.7 macrophages". Molecular Medicine Reports 19, no. 1 (2019): 629-637. https://doi.org/10.3892/mmr.2018.9678