TY - JOUR
T1 - Synergistic induction of inflammation by bacterial products lipopolysaccharide and fMLP
T2 - An important microbial pathogenic mechanism
AU - Chen, Ling Yu
AU - Pan, Warren W.
AU - Chen, Miao
AU - Li, Jain Dong
AU - Liu, Wei
AU - Chen, Guoqiang
AU - Huang, Shuang
AU - Papadimos, Thomas J.
AU - Pan, Zhixing K.
PY - 2009/2/15
Y1 - 2009/2/15
N2 - A wide variety of stimuli have been shown to induce inflammation, but bacteria products/components are considered the major inducers during bacterial infections. We previously demonstrated that bacterial products/components such as LPS, a glycolipid component of the bacterial outer membrane, and formylated peptides (fMLP), a bacterial-derived peptide, induced proinflammatory cytokine gene expression in human peripheral blood monocytes. We now present evidence that mixtures of bacterial products/components LPS and fMLP behave synergistically in the induction of inflammation in vitro and in vivo. Furthermore, our results indicate that the TLR4 and the IKKβ- IκBα signaling pathways are involved in the synergistic induction of inflammatory cytokines. The mechanism of synergistic activation of NF-κB is depended on nuclear translocation of p65 and phosphorylation of p65 at both Ser536 and Ser276 sites. These results demonstrate an important role for bacterial products/components from lysed bacteria in the pathogenesis of infectious diseases. We believe that this synergistic induction of inflammation by bacterial products LPS and fMLP represents an important pathogenic mechanism during bacterial infection, which may suggest novel therapeutic strategies or targets to minimize host injury following bacterial infection.
AB - A wide variety of stimuli have been shown to induce inflammation, but bacteria products/components are considered the major inducers during bacterial infections. We previously demonstrated that bacterial products/components such as LPS, a glycolipid component of the bacterial outer membrane, and formylated peptides (fMLP), a bacterial-derived peptide, induced proinflammatory cytokine gene expression in human peripheral blood monocytes. We now present evidence that mixtures of bacterial products/components LPS and fMLP behave synergistically in the induction of inflammation in vitro and in vivo. Furthermore, our results indicate that the TLR4 and the IKKβ- IκBα signaling pathways are involved in the synergistic induction of inflammatory cytokines. The mechanism of synergistic activation of NF-κB is depended on nuclear translocation of p65 and phosphorylation of p65 at both Ser536 and Ser276 sites. These results demonstrate an important role for bacterial products/components from lysed bacteria in the pathogenesis of infectious diseases. We believe that this synergistic induction of inflammation by bacterial products LPS and fMLP represents an important pathogenic mechanism during bacterial infection, which may suggest novel therapeutic strategies or targets to minimize host injury following bacterial infection.
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U2 - 10.4049/jimmunol.0713933
DO - 10.4049/jimmunol.0713933
M3 - Article
C2 - 19201908
AN - SCOPUS:61449238091
SN - 0022-1767
VL - 182
SP - 2518
EP - 2524
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -