Selected azaphenothiazines inhibit delayed type hypersensitivity and carrageenan reaction in mice.

Several, previously selected azaphenothiazines, as strongly antiproliferative agents in in vitro models, were subjected to evaluation for their potential immunosuppressive effects in the model of delayed type hypersensitivity (DTH) to ovalbumin (OVA) in BALB/c mice and in foot pad inflammation induced by carrageenan in CBA mice. In the DTH model the compounds were given to mice intraperitoneally (i.p.) in 50µg or 250µg doses, 1h before the elicitation of the response. In the carrageenan-induced foot pad inflammation the compounds were given i.p. in 50µg or 250µg doses, 24h and 2h before administration of carrageenan. Among the compounds, the significantly suppressive activities in both models were exhibited only by compound 5 (6-chloroethylureidoethyldiquino[3,2-b;2',3'-e][1,4]thiazine) and compound 4 (6-acetylaminobutyl-9-chloroquino[3,2-b]benzo[1,4]thiazine). Structure-activity relationship, plausible mechanism of action and potential application in therapy of the compounds are discussed.

Osteoinductive properties of urothelium depend on inherent bone morphogenetic proteins (BMPs).

BACKGROUND: The mechanism of heterotopic ossicle formation induced by grafted transitional epithelium, described in several species, has not yet been elucidated. This phenomenon is not species specific, but in xenogeneic systems, immunosuppression of the host is needed to protect the implant long enough for it to exert its osteoinductive potency. We showed a strong correlation between the intensity of bone induction caused by implantation of HeLa cell lines and their ability to synthesize and secrete seven different isoforms of BMPs (bone morphogenetic proteins). We decided to discover whether the urothelium of guinea pig, having high osteoinductive potency, differs in BMP content from human urothelium, which does not induce heterotopic bone. MATERIAL/METHODS: The RT-PCR technique was used to investigate the expression of BMP family genes. PCR products were directly sequenced with an ABI Prism 310 sequencer. The obtained sequences were analyzed using BLAST. RESULTS: Two isoforms of BMP (BMP-3 and BMP-4) were detected in the guinea pig urinary bladder mucosa. The sequences of these products were identified by BLAST analysis and compared with human mRNA and protein. The experiment performed on human urinary bladder mucosa failed to detect the expression of these BMPs, while b-actin mRNA was detected. CONCLUSIONS: Our findings explain the reason for the osteoinductive properties of guinea pig urothelium and are in line with the explanation of the osteoinductive properties of HeLa cells. Moreover, human urothelium, which did not express any BMP mRNA, therefore probably lacks osteoinductive competence.