Clostridium difficile toxins influence hepatocyte protein synthesis through the interleukin 1 receptor.
OBJECTIVE
Clostridium difficile toxins require interleukin 1 (IL-1) production or a functioning IL-1 receptor to elicit acute-phase protein production by murine hepatocytes.


METHODS
Experimental study.


METHODS
Research laboratory at the DVA Medical Center, St Louis, Mo. CELLS STUDIED: Hepatocytes prepared from normal mice, from knockout mice deficient in IL-1 production due to loss of IL-1 converting enzyme, or from knockout mice deficient in the IL-1 p80 receptor.


METHODS
Cells were treated with lipopolysaccharide, a crude C difficile toxin extract, or purified C difficile toxins A or B for 24 hours in vitro, then radiolabeled with (35)S methionine. Newly synthesized acute-phase proteins were identified by electrophoresis and autoradiography.


METHODS
Synthesis of a 23-kd acute-phase protein in response to the various stimuli.


RESULTS
Lipopolysaccharide, C difficile culture extract, and purified toxins A and B stimulated the synthesis of the 23-kd acute-phase protein by hepatocytes from normal mice and by hepatocytes from knockout mice deficient in the IL-1 converting enzyme. However, hepatocytes from knockout mice deficient in the IL-1 p80 receptor failed to produce this acute-phase protein when treated with the C difficile toxins, although they responded fully to lipopolysaccharide.


CONCLUSIONS
Stimulation of acute-phase protein synthesis by C difficile toxins does not require IL-1 production, but does require a functioning IL-1 p80 receptor. This suggests that some of the actions of these toxins are mediated by this receptor.
Mazuski
J E
JE
Department of Surgery, Saint Louis University School of Medicine, 3635 Vista Ave at Grand Boulevard, PO Box 15250, St Louis, MO 63110-0250, USA. mazuskim@slu.edu
Grossmann
E M
EM
Norman
J G
JG
Denham
W
W
Panesar
N
N
Shapiro
M J
MJ
Durham
R L
RL
Kaminski
D L
DL
Longo
W E
WE
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000818:Animals; D001345:Autoradiography; D001427:Bacterial Toxins / Q000494:pharmacology*; D002478:Cells, Cultured; D016360:Clostridioides difficile; D004586:Electrophoresis; D005260:Female; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity
D000209:Acute-Phase Proteins; D001427:Bacterial Toxins; D007375:Interleukin-1; D017472:Receptors, Interleukin-1