RESUMEN
Prostate development and function are regulated by androgens. Epithelial cell apoptosis in response to androgen deprivation is caspase-9-dependent and peaks at Day 3 after castration. However, isolated epithelial cells survive in the absence of androgens. Znf142 showed an on-off expression pattern in intraepithelial CD68-positive macrophages, with the on-phase at Day 3 after castration. Rats treated with gadolinium chloride to deplete macrophages showed a significant drop in apoptosis, suggesting a causal relationship between macrophages and epithelial cell apoptosis. Intraepithelial M1-polarization was also limited to Day 3, and the inducible nitric oxide synthase (iNOS) knockout mice showed significantly less apoptosis than wild-type controls. The epithelial cells showed focal DNA double-strand breaks (DSB), 8-oxoguanine, and protein tyrosine-nitrosylation, fingerprints of exposure to peroxinitrite. Cultured epithelial cells induced M1-polarization and showed focal DSB and underwent apoptosis. The same phenomena were reproduced in LNCaP cells cocultured with Raw 264.7 macrophages. In conclusion, the M1 142 -macrophage (named after Znf142) attack causes activation of the intrinsic apoptosis pathway in epithelial cells after castration.
Asunto(s)
Apoptosis/fisiología , Células Epiteliales/metabolismo , Macrófagos/fisiología , Estrés Oxidativo/fisiología , Próstata/patología , Antagonistas de Andrógenos , Andrógenos/metabolismo , Animales , Línea Celular , Gadolinio/farmacología , Masculino , Ratones , Ratones Noqueados , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/genética , Próstata/citología , Próstata/crecimiento & desarrollo , Neoplasias de la Próstata/patología , Células RAW 264.7 , Ratas , Ratas Wistar , Transactivadores/metabolismo , Factores de TranscripciónRESUMEN
Mucosal immunity defines the relationship of surfaces in contact with the environment and integrates diverse tissues such as epidermis, gum, nose, gut, uterus and prostate with the immune system. Although considered part of a system, each mucosa presents specific immune features beyond the barrier and secretory functions. Information regarding the mucosal immunology of the male reproductive tract and the prostate gland in particular is scarce. In this review, we approach the prostate as an epithelial barrier and as part of the mucosal immune system. Finally, we also raise a series of questions that will improve the understanding of this gland, its role in reproduction and its sensitivity/resistance to disease.