RESUMEN
BACKGROUND: Elevated systemic levels of pro-inflammatory cytokines cause hypotension during septic shock and induce capillary leakage in acute lung injury. Manassantin B has anti-inflammatory and anti-plasmoidal properties. This study examined the effects of manassantin B on lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages. METHODS: RAW 264.7 macrophage cells were incubated without or with (1, 3 and 10 microM) manassantin B and without or with (100 ng/ml) LPS. Manassantin B dissolved in phosphate buffered saline was added to the medium 1 h prior to the addition of LPS. The degree of activation of mitogen-activated protein kinase (MAPK) including extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun amino terminal kinases (JNK) and p38 MAPK, and the level of interleukin (IL)-1beta were determined 30 min and 24 h after the addition of LPS respectively. RESULTS: Manassantin B inhibited the production of IL-1beta and attenuated the phosphorylations of ERK1/2 and p38 MAPK, but not that of JNK, in RAW 264.7 cells treated with LPS. CONCLUSIONS: Manassantin B reduces LPS-induced IL-1beta expression through effects on ERK1/2- and p38 MAPK-mediated pathways. Manassantin B has potential as a potent anti-inflammatory drug for use in pathological processes such as sepsis or acute lung injury.