Abstract
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.
Highlights
A number of microbial cell wall products, including lipopolysaccharide, peptidoglycan fragments, lipoteichoic acid, and lipoproteins, have been demonstrated to activate macrophages [1]
1 The abbreviations used are: LAMP, lipid-associated mycoplasma proteins; LAMPf, M. fermentans-derived LAMP; MAPK, mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase; JNK, c-Jun NH2-terminal kinase; AP-1, activated protein 1; TNF␣, tumor necrosis factor ␣; PTX, pertussis toxin; SAPK, stress-activated protein kinase; PAGE, polyacrylamide gel electrophoresis; CRIB, Cdc42/Rac interactive binding; GST, glutathione S-transferase; C3Ia, C3 Iotathe activation of macrophages leading to the secretion of proinflammatory cytokines [6, 7]
MAPK pathways and NF-B and AP-1 play a crucial role in the activation of macrophages by LAMPf [8, 9], yet the upstream effectors involved in the LAMPf-mediated induction activation still have to be determined
Summary
A number of microbial cell wall products, including lipopolysaccharide, peptidoglycan fragments, lipoteichoic acid, and lipoproteins, have been demonstrated to activate macrophages [1]. 1 The abbreviations used are: LAMP, lipid-associated mycoplasma proteins; LAMPf, M. fermentans-derived LAMP; MAPK, mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase; JNK, c-Jun NH2-terminal kinase; AP-1, activated protein 1; TNF␣, tumor necrosis factor ␣; PTX, pertussis toxin; SAPK, stress-activated protein kinase; PAGE, polyacrylamide gel electrophoresis; CRIB, Cdc42/Rac interactive binding; GST, glutathione S-transferase; C3Ia, C3 Iotathe activation of macrophages leading to the secretion of proinflammatory cytokines [6, 7].
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