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

Song,Yoo‑Jeong; Kim,Ahyeon; Kim,Goon‑Tae; Yu,Han  Young; Lee,Eun‑So; Park,Mi  Jin; Kim,Young‑Jun; Shim,Soon‑Mi; Park,Tae‑Sik

doi:10.3892/mmr.2018.9678

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
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Affiliations: Department of Life Science, Gachon University, Sungnam, Gyeonggi 13120, Republic of Korea, Department of Dermatology, Ajou University School of Medicine, Suwon, Gyeonggi 16499, Republic of Korea, Department of Food and Biotechnology, Korea University, Sejong 30019, Republic of Korea, Department of Food Science and Technology, Sejong University, Seoul 05006, Republic of Korea
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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