Valnemulin downregulates nitric oxide, prostaglandin E sub(2), and cytokine production via inhibition of NF-[kappa]B and MAPK activity

• Published in: International immunopharmacology Vol. 9; no. 7-8; pp. 810 - 816
• Main Authors: Zhang, Xuemei, Li, Hongyu, Feng, Haihua, Xiong, Huanzhang, Zhang, Lei, Song, Yu, Yu, Lu, Deng, Xuming
• Format: Journal Article
• Language: English
• Published: 01.07.2009
• ISSN: 1567-5769
• DOI: 10.1016/j.intimp.2009.02.018

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 E sub(2) (PGE sub(2)), 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-[kappa]B 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.