hymecromone and Lupus-Erythematosus--Systemic

Hyaluronic acid (HA), a component of the extracellular matrix, is the ligand for CD44 and has been implicated in the pathogenesis of kidney inflammation in patients with systemic lupus erythematosus (SLE), but its direct role and mechanism of action have not been studied. Here we show that administration of hymecromone (4-Methylumbelliferone, 4-MU), an HA synthesis inhibitor, to lupus-prone mice suppressed dramatically lupus-related pathology. Interestingly, 4-MU stopped the appearance of disease when administered prior to its onset and inhibited the progression of disease when administered after its appearance. Inhibition of HA synthesis

Topics: Adult; Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Humans; Hyaluronan Receptors; Hyaluronic Acid; Hymecromone; Indicators and Reagents; Kidney; Leukocytes, Mononuclear; Lupus Erythematosus, Systemic; Male; Mice, Inbred MRL lpr; rho-Associated Kinases; Skin

An enzyme-linked immunosorbent assay is described for the assay of anti-DNA antibodies. The method employs plastic surface for immobilization of the antigen and alkaline phosphatase-linked rabbit anti-human IgG for the detection of immune complex using PNP-P and 4MU-P as substrates. The sensitivity of the assay increased by as much as 16-fold when fluorogenic substrate was used instead of conventional PNP-P and could therefore be employed for the detection of low avidity antibodies. Using PNP-P as substrate 57% of SLE patients were positive for DNA antibody, but if 4MU-P was introduced as substrate, 71% gave a positive response. Moreover, using a fluorogenic substrate, it was possible to minimise the amount of antigen (2 nM bp). The technique is simple, reproducible and of high sensitivity.

Topics: Alkaline Phosphatase; Animals; Antibodies, Antinuclear; Cattle; Chromogenic Compounds; DNA; Enzyme-Linked Immunosorbent Assay; Humans; Hymecromone; Lupus Erythematosus, Systemic; Nitrophenols; Rabbits; Substrate Specificity; Umbelliferones