Involvement of small GTPases in Mycoplasma fermentans membrane lipoproteins-mediated activation of macrophages.
Mycoplasma fermentans lipoproteins (LAMPf) are capable of activating macrophages and inducing the secretion of proinflammatory cytokines. We have recently reported that mitogen-activated protein kinase (MAPK) pathways and NF-kappaB and activated protein 1 (AP-1) play a crucial role in the activation induced by this bacterial compound. To further elucidate the mechanisms by which LAMPf mediate the activation of macrophages, we assessed the effects of inhibiting small G proteins Rac, Cdc42, and Rho. The Rho-specific inhibitor C3 enzyme completely abolished the secretion of tumor necrosis factor alpha by macrophages stimulated with LAMPf and also inhibited the activation of extracellular signal-regulated kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38 kinase. In addition, we have shown that LAMPf stimulate Cdc42 and that inhibition of Cdc42 or Rac by dominant negative mutants abrogates LAMPf-mediated activation of JNK and transactivation of NF-kappaB and AP-1 in the murine macrophage cell line RAW 264.7. These results indicate that small G proteins Rho, Cdc42, and Rac are involved in the cascade of events leading to the macrophage activation by mycoplasma lipoproteins.
Rawadi
G
G
Laboratoire des Mycoplasmes, Institut Pasteur, 25 Rue Docteur Roux, 75724 Paris Cedex 15, France. georges.rawadi@hmrag.com
Zugaza
J L
JL
Lemercier
B
B
Marvaud
J C
JC
Popoff
M
M
Bertoglio
J
J
Roman-Roman
S
S
D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D008074:Lipoproteins / Q000494:pharmacology*; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D016858:Mycoplasma fermentans / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D001427:Bacterial Toxins; D020690:GTPase-Activating Proteins; D008074:Lipoproteins; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D020558:GTP Phosphohydrolases; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins