title: Role of cAMP in interleukin-1-induced kappa light chain gene expression in murine B cell line.
abstract: The murine lymphoid cell line 70Z/3 has been extensively used to study the intracellular mechanisms of interleukin-1 (IL-1) action. In these cells IL-1 is known to induce kappa gene expression but the signal transduction pathway has yet to be defined. IL-1-induced kappa expression is associated with stimulation of Na+/H+ exchange and activation of protein kinase C, but these events are not sufficient to trigger kappa expression. Thus, other signals must be present. Because cAMP is a well recognized second messenger, we sought to determine whether cAMP is the signal that triggers IL-1-induced kappa expression. To that end we first measured intracellular levels of cAMP following IL-1 treatment. The results showed that exposure of 70Z/3 cells to IL-1 alpha induced a rapid and a transient increase in cAMP, it peaked at 5 min and was back to base-line level at 20 min. Prostaglandin E2 (PGE2) also increased cAMP with similar kinetics to IL-1 alpha but the increased levels were far greater. IL-1 alpha-induced increase in cAMP proved not be a sufficient signal because an increase in intracellular cAMP by N6,O2'-dibutyryl cAMP (Bt2cAMP) or PGE2 failed to increase surface IgM or to increase kappa mRNA level. Although when used alone they had no effect, Bt2cAMP and PGE2 were found to amplify the IL-1 alpha-induced kappa expression. IL-1 alpha transiently activated NF-kappa B transcription factor. But this effect could not be simulated by Bt2cAMP or PGE2. This observation provides further evidence that cAMP is not a trigger of kappa expression. Although Bt2cAMP or PGE2 when used alone had no effect, they did consistently modify the level of NF-kappa B activity induced by IL-1 alpha. Results of this study show that cAMP is not sufficient to induce NF-kappa B or kappa expression. Therefore, the role of cAMP may not be trigger but rather to modulate the IL-1 alpha-induced kappa expression. Regulation of the response could occur at one or a number of points along the signal pathway. Such a regulatory role is supported by the observation that cAMP modulates the IL-1 alpha-induced NF-kappa B activity.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195.
authors.forename: K
authors.initials: K
authors.lastname: Bomsztyk
authors.forename: B
authors.initials: B
authors.lastname: Toivola
authors.forename: D W
authors.initials: DW
authors.lastname: Emery
authors.forename: J W
authors.initials: JW
authors.lastname: Rooney
authors.forename: S K
authors.initials: SK
authors.lastname: Dower
authors.forename: N A
authors.initials: NA
authors.lastname: Rachie
authors.forename: C H
authors.initials: CH
authors.lastname: Sibley
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D015232:Dinoprostone / Q000494:pharmacology; D015870:Gene Expression; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D007145:Immunoglobulin kappa-Chains; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D014157:Transcription Factors; D003994:Bucladesine; D000242:Cyclic AMP; D015232:Dinoprostone