ADP-ribosylation: role in LPS-induced phosphorylation of two cytosolic proteins (p36/38) in monocytes.
Human monocytes respond to LPS by releasing proinflammatory cytokines such as TNF-alpha, IL-1 and IL-6. Here we show that inhibitors of ADP-ribosylation namely nicotinamide and meta-iodobenzylguanidine prevent production of TNF-alpha and IL-6 at the protein and mRNA level. The inhibitors also influence the LPS-induced phosphorylation pattern of cytosolic proteins. They consistently lead to changes of the phosphorylation state of two proteins with an apparent molecular mass of 36 kDa and 38 kDa. The changes are both time and dose dependent. The data suggest that the conditions leading to altered phosphorylation of p36/38 may correlate with conditions initiating and regulating TNF-alpha and IL-6 production.
Hauschildt
S
S
Department of Immunobiology, University of Leipzig, Germany.
Ulmer
A J
AJ
Flad
H D
HD
Heyden
T
T
Heine
H
H
D019797:3-Iodobenzylguanidine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009536:Niacinamide / Q000494:pharmacology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001798:Blood Proteins; D016207:Cytokines; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; D019797:3-Iodobenzylguanidine