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Enhanced expression of nucleobindin in lymphatic organs of lupus-prone mice

The First Department of Internal Medicine, Tokyo Medical and Dental University

T. Kubota

School of Allied Health Sciences, Faculty of Medicine, Tokyo Medical and Dental University, Tokyo

F. Satake

School of Allied Health Sciences, Faculty of Medicine, Tokyo Medical and Dental University, Tokyo

G. Hirokawa

School of Allied Health Sciences, Faculty of Medicine, Tokyo Medical and Dental University, Tokyo

K. Miura

Institute for Comprehensive Medical Science, Fujita Health University, Toyoake

Y. Kurosawa

Institute for Comprehensive Medical Science, Fujita Health University, Toyoake

N. Miyasaka

The First Department of Internal Medicine, Tokyo Medical and Dental University

Y. Kanai

Department of Molecular Oncology, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Nucleobindin (Nuc) was originally identified as a 55 kDa protein that enhanced anti-DNA antibody production in cultures of autoimmune MRL/lpr mouse spleen cells. cDNA cloning and the production of recombinant protein (rNuc) have revealed that rNuc binds to DNA and Ca²⁺ by means of leucine zipper and EF-hand motif structures. In vitro and in vivo effects of rNuc to induce autoantibodies including anti-dsDNA antibody in normal mice have been demonstrated; however, whether Nuc is involved in the state of autoimmunity occurred in MRL/ lpr, C3H/gld and male BXSB mice has not been elucidated. Here we report that the expression of Nuc mRNA is upregulated with age in the lymphatic organs and is positively correlated to the serum levels of Nuc in these lupus-prone strains of mice. Upon immunization with KLH in Freund's complete adjuvant, normal BALB/c mice also showed an elevated level of Nuc in their serum and elevated Nuc mRNA in their lymphatic organs. In addition, in vitro stimulation of BALB/c splenocytes with Con A or LPS remarkably enhanced Nuc mRNA expression. These results suggest that upregulation of Nuc mRNA in lymphatic organs and serum Nuc of lupus-prone mice is related to spontaneous activation of immunocompetent cells; the present data are also consistent with our previous hypothesis on the role of Nuc in the induction or enhancement of autoimmunity in lupus models of mice.

Key Words: nucleobindin • DNA binding protein • systemic lupus erythematosus • MRL/Mp-lpr/lpr mice • anti-DNA antibody

Lupus, Vol. 6, No. 4, 365-370 (1997)
DOI: 10.1177/096120339700600404


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