Showing papers by "Shizuo Akira published in 1990"

A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family.

Abstract: NF-IL6 is a nuclear factor that specifically binds to an IL1-responsive element in the IL-6 gene. In this study the gene encoding NF-IL6 has been cloned by direct screening of a lambda gt11 library using NF-IL6 binding sequence as a ligand. The full-length cDNA encoded a 345 amino acid protein with a potential leucine zipper structure and revealed a high degree of homology to a liver-specific transcriptional factor, C/EBP, at the C-terminal portion. The bacterial fusion protein bound to the CCAAT homology as well as the viral enhancer core sequences as in the case of C/EBP. Recombinant NF-IL6 activated the human IL-6 promoter in a sequence-specific manner. Southern blot analysis demonstrated the high-degree conservation of the NF-IL6 gene through evolution and the existence of several other related genes sharing the DNA-binding domain. NF-IL6 mRNA was normally not expressed, but induced by the stimulation with either LPS, IL-1 or IL-6. Interestingly, NF-IL6 was shown to bind to the regulatory regions for various acute-phase protein genes and several other cytokine genes such as TNF, IL-8 and G-CSF, implying that NF-IL6 has a role in regulation not only for the IL-6 gene but also for several other genes involved in acute-phase reaction, inflammation and hemopoiesis.

Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF).

Abstract: Interleukin 1 (IL 1), IL 6, and tumor necrosis factor (TNF) are typical examples of multifunctional cytokines involved in the regulation of the immune response, hematopoiesis, and inflammation. Their functions are widely overlapping but each shows its own characteristic properties. IL 6 was originally identified as a B cell differentiation factor, and thus one of the major functions of IL 6 is antibody induction. Transgenic mice have provided much needed information on the pathophysiological role of cytokines. With IL 6 transgenic mice, deregulation of the IL 6 expression was suggested to be involved in the generation of plasmacytoma/myeloma and mesangium proliferative glomerulonephritis. The cis-regulatory elements and trans-acting nuclear factor (or factors) for the IL 6 expression (NF-IL 6) have been identified. NF-IL 6 was shown to be a member of a C/EBP family, and the possible involvement of NF-IL 6 not only in the IL 6 regulation but also in the induction of various acute phase proteins was also ob...

Constitutive and interleukin-1 (IL-1)-inducible factors interact with the IL-1-responsive element in the IL-6 gene.

Abstract: The interleukin-6 (IL-6) promoter is rapidly and transiently activated with other cytokines, including IL-1, tumor necrosis factor, and platelet-derived growth factor, as well as phorbol esters and agents that increase intracellular cyclic AMP. In this study, we have investigated cis-acting regulatory elements and trans-acting factors responsible for IL-1-induced IL-6 gene expression. Studies on the 5' deletion mutants of the human IL-6 gene suggested that the IL-1-responsive element was mapped within the IL-6 promoter region (-180 to -123) which was homologous to the c-fos serum-responsive enhancer element. Gel retardation assay identified two types of nuclear factors that bound to this region, one constitutive and the other inducible. These two factors recognized a 14-base-pair (bp) palindromic sequence, ACATTGCACAATCT. Furthermore, three copies of this 14-bp palindrome conferred IL-1 responsiveness to the basal enhancerless IL-6 promoter, indicating that a 14-bp-dyad symmetry sequence was an IL-1-responsive element in the IL-6 gene.

Biological and clinical aspects of

Abstract: 33 Tony, H-P., Phillips, N.E. and Parker, E..C. (1985)J. Exp. Med. 162, 1695 1708 34 Kupfer, A. and Singer, S.J. (1989) J. Exp. Med. 170, 1697--1713 35 Watanabe, M., Wegma, D.R., Ochi, A. and Hozumi, N. (1986) Proc. Natl Acad. Sci. USA 83, 5247 5251 36 Bonnefoy, J.Y., Guillot, O., Spits, H. etal. (1988) J. Exp. Med. 167, 57 72 37 Lee, W.T., Rao, M and Conrad, D.H (1987) ./. Immunoi 139,1191 1198 38 MacLennan, I.C.M. and Gray, D. (1936)Immunol. Rev. 91, 61 85 39 Liu, Y-J., Joshua, D.E., Williams, G.T. et al. (1989)Nature 342,929 931 40 Reynes, M., Aubert, J-P., Cohen, J.H.M. etal. (1985) J. Imrnunol. 135, 2687 2694 41 Johnson, G.D., MacLennan, I.C.M., Ling, N.R. and Hardie, L. (1987)in Leukocyte I-yping III (McM0chael, A.J. et al., eds). p. 387, Oxford University Press 42 Sellheyer, K., <"~ .... ;"~ -," ~;J9 R. and Steln, 11. (1989) C/in £xp Immunol. 78, 431 436 43 Swendeman, S. and 1-horley Lawson, D A (1987) EMBO J 6,1637 1642 44 Gordon, J., Cairns, J.A, Millsum, M.J., Gillb, S. and Guy, G.R. (1988) Eur. 2. Irnmunol. 18, 156! 1565 45 Uchibayashi, N, Kikutani, H., Barsumian. E_L. et al (1989) J. Immunol. 142, 3901 3908 46 Fanger, M.W., Shen, L., Ora,iano, R.F. and Guyre, P.M (1989) Immunol. Today 1 O, 92 99 47 Kikutani, H., Invi, S., Sato, R. etal. (1986) Ce1147, 651 665 48 Phillips, N.E. and Parker, D C (1984)J. Immunol. 132, 627 632 49 Miettinen, H.M., Rose, JK ar,4 Mellman, I (1989) Cell 58, 317 327