Effect Of 9-cis Retinoic Acid Research Articles

Effects of 13-Cis Retinoic Acid Therapy on Human Antibody Responses to Defined Protein Antigens

We have evaluated the in vivo effects of 13-cis retinoic acid (13-cis RA) on human antibody responses to immunization with tetanus toxoid (TT) and keyhole limpet hemocyanin (KLH). Subjects with severe cystic acne were immunized with suboptimal doses (10 micrograms) of KLH 7 d and 3 months after starting retinoid therapy (13-cis RA, 1 mg/kg/day for 4 mo). A standard booster immunization with TT was given along with the initial KLH sensitization. A control group of acne patients received identical immunization regimens, but no 13-cis RA. Plasma retinoid levels were evaluated by reverse-phase HPLC and confirmed that blood-level concentrations of 13-cis RA and metabolites in these acne patients reached values previously demonstrated to be immunomodulatory in vitro. The retinoid had no effect on responses to TT as reflected by the characteristics of increased anti-TT IgG levels or the isotype distribution of the antibody. In contrast, the anti-KLH response was significantly enhanced in the 13-cis-RA-treated group. Whereas anti-KLH antibody was detected in only 4 of 13 control subjects after the secondary immunization, 10 of 13 retinoid-treated subjects had measurable levels of anti-KLH IgG (p less than 0.05). Among the responders, no differences were noted in the isotype distribution of anti-KLH antibody. These results showing enhanced anti-KLH responses induced by 13-cis RA therapy represent the first demonstration in humans that in vivo administration of a retinoid can modulate antigen-specific immune responses.

Organ maintenance of human sebaceous glands: in vitro effects of 13-cis retinoic acid and testosterone

Human sebaceous glands were isolated by shearing, and maintained for 7 days either on defined medium, on medium supplemented with 3 microM-testosterone or on medium supplemented with both 3 microM-testosterone and 1 microM-13-cis retinoic acid. Freshly isolated glands retained their in vivo morphology. On maintenance, the glands retained their freshly isolated rates of cell division, but the sebocytes showed increased keratinization and there was multilayering of the peripheral undifferentiated cells. However, glands maintained in the presence of 1 microM-13-cis retinoic acid showed very little luminal keratinization and only a small degree of multilayering. On autoradiography, freshly isolated glands retained their in vivo pattern of [methyl-3H]thymidine incorporation. Similar patterns were seen when glands were maintained for 7 days with or without testosterone. However, in the presence of both testosterone and 13-cis retinoic acid there was only slight graining. Following 7 days maintenance the rate of lipogenesis fell significantly. This was partially reversed by testosterone, but further inhibited by 13-cis retinoic acid. The patterns of lipids that are synthesised after a week's maintenance are very similar to those seen in freshly isolated glands, except that the squalene:cholesterol ratio is reversibly regulated by 3 microM-testosterone and 1 microM-retinoic acid. Protein synthesis was maintained at the same rates as for freshly isolated glands under all conditions of maintenance. Whereas DNA synthetic rates were maintained in the presence of testosterone, they were significantly inhibited by 13-cis retinoic acid. Glandular wet weights were retained under all conditions of maintenance, except that they were significantly reduced by 13-cis retinoic acid. This study shows that human sebocytes continue to divide on organ maintenance, but that they do not differentiate fully. However, this provides the first demonstration that 13-cis retinoic acid acts on human sebaceous glands directly, reducing the rate of cell division and the rate of lipogenesis, which shows that the maintained human sebaceous gland might provide a useful model for studying the effect of 13-cis retinoic acid on human sebocytes.

Effect of 13-Cis retinoic acid on cystic acne in Singapore

Effect of 13-Cis retinoic acid on cystic acne in Singapore

Immunomodulating effects of 13-cis retinoic acid on the IgG and IgM response of BALB/c mice.

The results reported here provide information on the effects of 13-cis retinoic acid (13-cRA) on the IgG and IgM responses in BALB/c mice. For these studies, a suboptimum immunizing concentration of ovalbumin (1 microgram) was used. BALB/c mice were given either 13-cRA or control beadlets (gel) as either 1 dose (at day -1) or 4 doses (at week -3, -2, -1, and day -1) prior to primary immunization, or 4 doses prior to, and 4 doses after, primary immunization (week -3, -2, -1, day -1, week 1, 2, 3, and day 27). The results consistently showed no primary antibody response and excellent secondary antibody levels in all 13-cRA-treated groups. Attempts to determine whether the 13-cRA affected the afferent or efferent phase of antibody induction by varying the time of the administration of a single 13-cRA dose, relative to immunization, showed no difference in the results in animals treated on day -2 to day 3.

Influence of 13-cis retinoic acid on zymosan-induced chemiluminescence of granulocytes

The effect of 13-cis retinoic acid (Ro-4-3780) on zymosan-induced chemiluminescence (CL) of freshly drawn human blood and isolated granulocytes has been examined in vitro. A marked enhancement was observed; optimal concentrations were 100 μg/ml in whole blood CL and 10 μg/ml in isolated granulocyte CL. It was found that already 5 μg/ml of 13-cis retinoic acid in isolated granulocytes showed a significant enhancement in zymosan-induced CL. The enhancement by 13-cis retinoic acid was completely inhibited by 10-5 M sodium azide, which is an inhibitor of myeloperoxidase activity. CL response was not enhanced by retinoic acid in mouse bone marrow originated cultured macrophages, which do not have myeloperoxidase activity. These findings strongly suggest that 13-cis retinoic acid might stimulate myeloperoxidase-dependent CL.