Interleukin 1 and cyclic AMP induce kappa immunoglobulin light-chain expression via activation of an NF-kappa B-like DNA-binding protein.

Abstract

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.

NF-kappa B-dependent induction of the NF-kappa B p50 subunit gene promoter underlies self-perpetuation of human immunodeficiency virus transcription in monocytic cells.

“…Further, the synergistic effect of PMA and HIV infection on the enhancement of p105 gene transcription indicates that these two stimuli use different, complementary transduction pathways. PKC-independent intracellular transduction pathways leading to NF-KB translocation have been described (14,(35)(36)(37). TNF upregulates two PKC-independent pathways, those dependent on phospholipase A2 hydrolysis and phosphatidylcholine-specific phospholipase C activity (38,39 (40), making it unlikely that HIV acts through these cytokines.…”

“…NF-KB is a heterodimer composed of 50-kDa (p50) and 65-kDa (p65) subunits (2-4), for which cDNAs have been cloned (5)(6)(7)(8)(9). In the majority of cells studied, NF-KB is present in an inactive form in the cytoplasm, bound through the p65 subunit to the inhibitory protein IKB (3,4,8,(10)(11)(12) and its phosphorylation by kinases prevents this inhibitory binding, allowing NF-KB to translocate to the nucleus (13,14). The deduced amino acid sequences of the p50 and p65 subunits show that they belong to the same multigene family as the c-rel protooncogene product (5,6,8,9).…”

Increased cyclic AMP levels enhance IL-1 alpha and IL-1 beta mRNA expression and protein production in human myelomonocytic cell lines and monocytes.

“…Possible DNA-binding proteins involved in this activation are c-Fos, Jun B, and NFKB. c-Fos and Jun B synthesis (35,36) and NFKB-binding activities (37) are stimulated by cAMP. c-Fos and Jun B form a heterodimer that activates gene transcription by binding to the ubiquitous AP-1 binding site.…”

Functional and physical associations between NF-kappa B and C/EBP family members: a Rel domain-bZIP interaction.

“…Thus, NF-KB subunits, which are strongly implicated in the control of cellular proliferation and are induced in the Go-to-G1 transition (7), may functionally stimulate c-fos gene expression when C/EBP is present. C/EBP is induced by compounds that activate cAMP (55), and evidence has been presented that increased cAMP levels may induce preexisting NF-KB as well (76,77). Thus, an increase in cAMP levels may coinduce C/EBP and NF-KB, allowing for enhanced expression from C/EBP binding sites and, potentially, a decrease in gene expression mediated by NF-KB binding sites.…”