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.
journal_name
Mol Med Repjournal_title
Molecular medicine reportsauthors
Song YJ,Kim A,Kim GT,Yu HY,Lee ES,Park MJ,Kim YJ,Shim SM,Park TSdoi
10.3892/mmr.2018.9678subject
Has Abstractpub_date
2019-01-01 00:00:00pages
629-637issue
1eissn
1791-2997issn
1791-3004journal_volume
19pub_type
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