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Progesterone has nongenomic effects on inducible nitric oxide synthase (iNOS), which is mediated by mitogen activated protein kinase (MAPK) pathways. This effect is supposed to have some potential association with asymptomatic gonococcal infections in women by immunological depression. In this study, polymorphonuclear leukocytes (PMNs) challenged by gonococci were used to study the nongenomic effects of progesterone. The activation of iNOS was assessed by measuring [(3)H] L-arginine converses to [(3)H] L-citrulline, and the activity of MAPK was detected by Western blot. It was found that the activity of iNOS and the yields of NO were enhanced significantly in gonococci-challenged PMNs compared with the controls (P0.01). Progesterone could repress the activation of iNOS through P38MAPK pathway within PMNs (P0.05), which could be blocked by SB203580 (P0.01), but not by actinomycin D (P0.05). It was also found subsequently that in the serum specimens collected from gonococci-infected but asymptomatic women, the progesterone level was higher than that in women with severe symptoms (P0.01). Moreover, the yield of NO had an inverse correlation with progesterone. With these results it suggested that the rapid nongenomic effects of progesterone may inhibit iNOS activation and NO yields mediated by P38MAPK pathways, which were supposed to be concerned with asymptomatic women infected with gonococci.

Background Genome-wide RNA interference screening study revealed that loss of expression of insulin-like growth factor binding protein 7 (IGFBP7) is a critical step in development of a malignant melanoma (MM), and this secreted protein plays a central role in apoptosis of MM. In this study we constructed pcDNA3.1-IGFBP7 to obtain high expression of IGBPF7 and to inhibit the growth of MM in C57BL/6J mice. Methods pcDNA3.1-IGFBP7 was transfected into B16-F10 cell, the expression of IGFBP7 was detected by RT-PCR and western blot. The proliferations and apoptosis rates of transfected and control cells were measured by CCK8 and FCM, respectively. The tumorigenicity and tumor growth in both pcDNA3.1-IGFBP7 group and control groups were studied in C57BL/6J mice model. IGFBP7, caspase-3, and VEGF expressions in tumor tissue were measured by immunohistochemistry. Apoptosis of tumors were detected by TUNEL. Results We demonstrated this plasmid inhibited proliferation of B16-F10 melanoma cells efficiently in vivo, exploiting the high expression of IGFBP7. More importantly, in-vivo transfection of pcDNA3.1-IGFBP7 inhibited MM growth in C57BL/6J mice. The inhibition of MM growth was proved owing to apoptosis and reduced expression of VEGF induced by pcDNA3.1-IGFBP7. Conclusions These results suggest a potential new clinical strategy for MM gene treatment.