The binding subunit of pertussis toxin inhibits IL-1 induction of IL-2 and prostaglandin production.
The inhibitory effect of pertussis toxin on the action of IL-1 has been investigated. The toxin inhibited IL-1-induced production of IL-2 mRNA and protein in EL4 cells. The B oligomer of the toxin, which was shown to be devoid of ADP-ribosylating activity, proved as inhibitory as the holotoxin. The inhibition was therefore attributable to the binding subunit of the toxin and not to its ability to ADP-ribosylate G proteins. The toxin did not affect the IL-1R binding to its ligand, nor did it inhibit an early post-receptor event, the induction of the transcription factor NF kappa B. This implied that the toxin was not uncoupling IL-1R signaling. The toxin, or its B oligomer, inhibited PGE2 synthesis in human gingival fibroblasts stimulated by IL-1, but not by PMA. Assay of PG synthetic activity in the cells after addition of exogenous arachidonic acid suggested impairment by the toxin of induction of PG-synthesizing enzymes. IL-1 stimulation of IL-6 or collagenase production by fibroblasts was unaffected by pertussis toxin. The binding subunit of the toxin inhibits certain IL-1 responses by virtue of previously unrecognized actions on lymphoid and fibroblastic cells. It does not appear to block early signaling and the inhibition highly unlikely to involve inactivation of a G protein.
O'Neill
L A
LA
Cytokine Biochemistry Group, Strangeways Research Laboratory, Worts' Causeway, Cambridge, U.K.
Ikebe
T
T
Sarsfield
S J
SJ
Saklatvala
J
J
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D019204:GTP-Binding Proteins / Q000502:physiology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D003012:Microbial Collagenase / Q000096:biosynthesis; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis; D037342:Pertussis Toxin; D011453:Prostaglandins / Q000096:biosynthesis*; D013945:Thymoma / Q000378:metabolism; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D016328:NF-kappa B; D011453:Prostaglandins; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D037342:Pertussis Toxin; D003012:Microbial Collagenase; D019204:GTP-Binding Proteins