Interleukin 1 and cyclic AMP induce kappa immunoglobulin light-chain expression via activation of an NF-kappa B-like DNA-binding protein.
Interleukin 1 (IL-1) induces the synthesis of kappa immunoglobulin light chains and the expression of surface immunoglobulin in the murine pre-B-cell line 70Z/3 (J. G. Giri, P. W. Kincade, and S. B. Mizel, J. Immunol. 132:223-228, 1984). In the present study, we found that these effects of IL-1 are mimicked by cyclic AMP (cAMP) analogs and cAMP-elevating drugs. The induction of kappa immunoglobulin light-chain gene expression by IL-1 was associated with an increase in intracellular cAMP levels. Incubation of 70Z/3 cells with IL-1 or cAMP resulted in the activation of the kappa immunoglobulin enhancer, as detected by the induction of chloramphenicol acetyltransferase (CAT) in cells transfected with a kappa enhancer-CAT expression plasmid. In contrast, CAT plasmids lacking a kappa immunoglobulin enhancer were inactive in the presence of IL-1 or cAMP. Furthermore, IL-1 and cAMP analogs and inducers were found to induce the activation of a NF-kappa B-like DNA-binding protein that exhibited specificity for the kappa immunoglobulin enhancer. These results suggest that cAMP may play an important role as a second messenger for IL-1 in the induction of kappa immunoglobulin light-chain synthesis in pre-B cells via the activation of a DNA-binding protein that is similar or identical to NF-kappa B.
Shirakawa
F
F
Department of Microbiology and Immunology, Wake Forest University Medical Center, Winston-Salem, North Carolina 27103.
Chedid
M
M
Suttles
J
J
Pollok
B A
BA
Mizel
S B
SB
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005803:Genes, Immunoglobulin / Q000187:drug effects*; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D007145:Immunoglobulin kappa-Chains; D007375:Interleukin-1; D016328:NF-kappa B; D014157:Transcription Factors; D000242:Cyclic AMP