Induction of cytokines and chemokines in human monocytes by 12 Mycoplasma fermentans-derived lipoprotein MALP-2

Bacterial infections are characterized by strong inflammatory reactions. Th e responsible mediators are often bacterially derived cell wall molecules, such as lipopolysaccharide or lipoteichoic acids, which typically stimulate monocytes and macrophages to release a wide variety of inflammatory cytoki nes and chemokines, Mycoplasmas, which lack a cell,wall, may also stimulate monocytes very efficiently. This study was performed to identify mycoplasm a-induced mediators. We investigated the induction of cytokines and chemoki nes in human monocytes exposed to the Mycoplasma fermentans-derived membran e component MALP-2 (macrophage-activating lipopeptide 2) by dose response a nd kinetic analysis. We found a rapid and strong MALP-2-inducible chemokine and cytokine gene expression which was followed by the release of chemokin es and cytokines with peak levels after 12 to 20 h, MALP-2; induced the neu trophil-attracting CXC chemokines interleukin-8 (IL-8) end GRO-alpha as wel l as the mononuclear leukocyte-attracting CC chemokines MCP-1, MIP-1 alpha, and MIP-1 beta. Production of the proinflammatory cytokines tumor necrosis factor alpha and IL-6 started at the same time as chemokine release but re quired 10- to 100-fold-higher MALP-2 doses. The data show that the mycoplas ma-derived lipopeptide MALP-2 represents a potent inducer of chemokines and cytokines which may, by the attraction and activation of neutrophils and m ononuclear leukocytes, significantly contribute to the inflammatory respons e during mycoplasma infection.