Retinoic acid--a player that rules the game of life and death in neutrophils.

Neutrophils are the most prevalent white blood cells in the circulation. They represent the first line of defense against invading microorganisms and have been implicated in the pathogenesis of a number of human diseases. In response to various factors, the pluripotent stem cells in bone marrow differentiate into mature neutrophils, enter the blood stream, and die within 24 hr via apoptosis. Numerous defects can occur during the process of neutrophils' differentiation that can manifest in the form of a variety of clinical disorders. Retinoids (Vitamin A and analogues), in general, and all-trans retinoic acid (tRA), in particular, play a critical role during differentiation of neutrophils. tRA can directly modulate gene expression via binding to its nuclear receptors, which in turn, can activate transcription of genes that are essential for differentiation of immature cells to neutrophils. Involvement of retinoic acid receptor in pathogenesis of acute promyelocytic leukemia (APL), reflects an important role played by this receptor in differentiation of immature myeloid cells to neutrophils. This review summarizes evidence on involvement of retinoic acid-mediated events in differentiation process of neutrophils and their subsequent apoptosis.

Effect of retinoic acid and peroxisome proliferate on the transfection of alfa-fetoprotein gene in human hepatoma cell lines

Retinoic acid [t-RNA] at concentration 1 uM led to deplete CAT gene activity induced by AFP 7300 plasmid transfection in Hep3B [B-virus integrated], whereas in Hu-h7 [non-viral type] the effect was just slight down-regulation of the gene activity. However, in the presence of proxisome proliferator [2 uM] complete absence of CAT reaction was clearly observed in this cell line [Hu-h7]. On the other hand, proxisome proliferator [PP] alone did not show any effect at all in the viral type cell line, [Hep3B], whereas in the non-viral type [Hu- h7], down-regulation of CAT gene function was clearly observed. Therefore, the response of the previous mentioned cell lines [viral and non-viral] either to t-RA or PP was absolutely different. The finding sheds a light on new avenues for differential useful therapy for patient suffering from hepatoma with different past-history of the disease