Nucleosomes contribute to increase mesangial cell chemokine expression during the development of lupus nephritis.

Nucleosomes represent a set of major autoantigens in the induction of systemic lupus erythematosus (SLE), and appear to be essential for the development of lupus nephritis. Deposition of nucleosome-containing immune complexes within the mesangial matrix and activation of mesangial cells may be important in the progression of lupus nephritis from a "sleeping" minimal change disease state to a full blown disease state. This study investigated the renal cytokine profile both in vivo during the development of the disease in (NZBxNZW)F1 (B/W) mice, and in vitro in primary B/W mesangial cells stimulated with nucleosomes, nucleosome-IgG complexes, and anti-dsDNA mAb respectively.

Heparin exerts a dual effect on murine lupus nephritis by enhancing enzymatic chromatin degradation and preventing chromatin binding in glomerular membranes.

Objective: Association of nucleosome-IgG immune complexes with glomerular basement membranes (GBMs) is an important event in the development of lupus nephritis. Preventing this binding and/or increasing nuclease sensitivity of nucleosomes may be viable strategies for the prevention of the disease. Theoretically, heparin may alter nucleosomal structure and increase sensitivity to proteinases and nucleases, and may also inhibit binding of nucleosomes and nucleosome-IgG complexes to basement membrane structures.

Anti-dsDNA antibodies promote initiation, and acquired loss of renal Dnase1 promotes progression of lupus nephritis in autoimmune (NZBxNZW)F1 mice.

Background: Lupus nephritis is characterized by deposition of chromatin fragment-IgG complexes in the mesangial matrix and glomerular basement membranes (GBM). The latter defines end-stage disease. METHODOLOGY/PRINCIPALS: In the present study we determined the impact of antibodies to dsDNA, renal Dnase1 and matrix metalloprotease (MMP) mRNA levels and enzyme activities on early and late events in murine lupus nephritis.

Molecular characterization of cold adaptation based on ortholog protein sequences from Vibrionaceae species.

A set of 298 protein families from psychrophilic Vibrio salmonicida was compiled to identify genotypic characteristics that discern it from orthologous sequences from the mesophilic Vibrio/Photobacterium branch of the gamma-Proteobacteria (Vibrionaceae family). In our comparative exploration we employed alignment based bioinformatical and statistical methods. Interesting information was found in the substitution matrices, and the pattern of asymmetries in the amino acid substitution process.