TY - JOUR
T1 - The bacterial quorum-sensing signal molecule N-3-oxo-dodecanoyl-L- homoserine lactone reciprocally modulates pro- and anti-inflammatory cytokines in activated macrophages
AU - Glucksam-Galnoy, Yifat
AU - Sananes, Roy
AU - Silberstein, Nava
AU - Krief, Pnina
AU - Kravchenko, Vladimir V.
AU - Meijler, Michael M.
AU - Zor, Tsaffrir
PY - 2013/7/1
Y1 - 2013/7/1
N2 - The bacterial molecule N-3-oxo-dodecanoyl-L-homoserine lactone (C12) has critical roles in both interbacterial communication and interkingdom signaling. The ability of C12 to downregulate production of the key proinflammatory cytokine TNF-α in stimulated macrophages was suggested to contribute to the establishment of chronic infections by opportunistic Gram-negative bacteria, such as Pseudomonas aeruginosa. We show that, in contrast to TNF-α suppression, C12 amplifies production of the major anti-inflammatory cytokine IL-10 in LPS-stimulated murine RAW264.7 macrophages, as well as peritoneal macrophages. Furthermore, C12 increased IL-10 mRNA levels and IL-10 promoter reporter activity in LPS-stimulated RAW264.7 macrophages, indicating that C12 modulates IL-10 expression at the transcriptional level. Finally, C12 substantially potentiated LPS-stimulated NF-κB DNA-binding levels and prolonged p38 MAPK phosphorylation in RAW264.7 macrophages, suggesting that increased transcriptional activity of NF-κB and/or p38-activated transcription factors serves to upregulate IL-10 production in macrophages exposed to both LPS and C12. These findings reveal another part of the complex array of host transitions through which opportunistic bacteria downregulate immune responses to flourish and establish a chronic infection.
AB - The bacterial molecule N-3-oxo-dodecanoyl-L-homoserine lactone (C12) has critical roles in both interbacterial communication and interkingdom signaling. The ability of C12 to downregulate production of the key proinflammatory cytokine TNF-α in stimulated macrophages was suggested to contribute to the establishment of chronic infections by opportunistic Gram-negative bacteria, such as Pseudomonas aeruginosa. We show that, in contrast to TNF-α suppression, C12 amplifies production of the major anti-inflammatory cytokine IL-10 in LPS-stimulated murine RAW264.7 macrophages, as well as peritoneal macrophages. Furthermore, C12 increased IL-10 mRNA levels and IL-10 promoter reporter activity in LPS-stimulated RAW264.7 macrophages, indicating that C12 modulates IL-10 expression at the transcriptional level. Finally, C12 substantially potentiated LPS-stimulated NF-κB DNA-binding levels and prolonged p38 MAPK phosphorylation in RAW264.7 macrophages, suggesting that increased transcriptional activity of NF-κB and/or p38-activated transcription factors serves to upregulate IL-10 production in macrophages exposed to both LPS and C12. These findings reveal another part of the complex array of host transitions through which opportunistic bacteria downregulate immune responses to flourish and establish a chronic infection.
UR - http://www.scopus.com/inward/record.url?scp=84879616964&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1300368
DO - 10.4049/jimmunol.1300368
M3 - Article
AN - SCOPUS:84879616964
SN - 0022-1767
VL - 191
SP - 337
EP - 344
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -