Inhibition of lactate dehydrogenase A suppresses inflammatory response in RAW 264.7 macrophages
- Authors
- 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
- Issue Date
- Jan-2019
- Publisher
- SPANDIDOS PUBL LTD
- Keywords
- lactate; inflammation; lactate dehydrogenase; mitogen-activated protein kinase; cytokines
- Citation
- MOLECULAR MEDICINE REPORTS, v.19, no.1, pp.629 - 637
- Journal Title
- MOLECULAR MEDICINE REPORTS
- Volume
- 19
- Number
- 1
- Start Page
- 629
- End Page
- 637
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/2008
- DOI
- 10.3892/mmr.2018.9678
- ISSN
- 1791-2997
- 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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