Valnemulin downregulates nitric oxide, prostaglandin E2, and cytokine production via inhibition of NF-kappaB and MAPK activity.
Valnemulin is a pleuromutilin antibiotic used in clinics for the treatment of various infections. We studied the in vitro anti-inflammatory effects of valnemulin and associated signal transduction mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that valnemulin inhibited nitric oxide (NO), prostaglandin E2 (PGE2), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and increased interleukin-10 (IL-10) production. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression were also inhibited by valnemulin. We further observed that valnemulin prevented the LPS-induced NF-kappaB translocation from the cytoplasm into the nucleus. Valnemulin also blocked phosphorylation of three mitogen-activated protein kinases (MAPKs): extracellular signal receptor-activated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK). Our data indicate that valnemulin may have therapeutic anti-inflammatory effects independent of its antibacterial activity.
Zhang
Xuemei
X
Institute of Zoonoses, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China.
Li
Hongyu
H
Feng
Haihua
H
Xiong
Huanzhang
H
Zhang
Lei
L
Song
Yu
Y
Yu
Lu
L
Deng
Xuming
X
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D016207:Cytokines; D004224:Diterpenes; D008070:Lipopolysaccharides; D016328:NF-kappa B; C117845:valnemulin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone