Valnemulin downregulates nitric oxide, prostaglandin E2, and cytokine production via inhibition of NF-kappaB and MAPK activity.

Abstract

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.

• Authors: Xuemei Zhang, Hongyu Li, Haihua Feng, Huanzhang Xiong, Lei Zhang, Yu Song, Lu Yu, Xuming Deng
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 9 Issue 7-8 Pg. 810-6 (Jul 2009) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 19293003 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Cytokines
• Diterpenes
• Lipopolysaccharides
• NF-kappa B
• valnemulin
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Extracellular Signal-Regulated MAP Kinases
• Dinoprostone

Topics

• Animals
• Anti-Bacterial Agents (administration & dosage)
• Cell Line
• Cyclooxygenase 2 (genetics, immunology, metabolism)
• Cytokines (genetics, immunology, metabolism)
• Dinoprostone (genetics, metabolism)
• Diterpenes (pharmacology)
• Down-Regulation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors)
• Lipopolysaccharides (metabolism)
• Macrophages (drug effects, metabolism, pathology)
• Mice
• NF-kappa B (antagonists & inhibitors)
• Nitric Oxide (genetics, metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)