Antimicrobial peptides of the vaginal innate immunity and their role in the fight against sexually transmitted diseases.

Some antimicrobial peptides (AMPs) are produced in the vaginal innate immune system and play an important role in protecting this organ against pathogenic agents. Moreover, sexually transmitted diseases have become a major problem in human societies and are rapidly spreading. The emergence of antibiotic-resistant microbes (superbugs) can pose a major threat to human societies and cause rapid spread of these diseases. Finding new antimicrobial compounds to fight superbugs is therefore essential. It has been shown that AMPs have good potential to become new antibiotics. The most important AMPs in the vaginal innate immune system are defensins, secretory leucocyte protease inhibitors, calprotectin, lysozyme, lactoferrin and elafin, which play an important role in host defence against sexually transmitted infections, modulation of immune responses and anticancer activities. Some AMPs, such as LL-37, magainin 2 and nisin, show both spermicidal and antimicrobial effects in the vagina. In this summary, we will discuss vaginal AMPs and continue to address some of the challenges of using peptides to control pathogens that are effective in sexually transmitted diseases.

Apoptosis, autophagy and ER stress in mevalonate cascade inhibition-induced cell death of human atrial fibroblasts.

3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) are cholesterol-lowering drugs that exert other cellular effects and underlie their beneficial health effects, including those associated with myocardial remodeling. We recently demonstrated that statins induces apoptosis and autophagy in human lung mesenchymal cells. Here, we extend our knowledge showing that statins simultaneously induces activation of the apoptosis, autophagy and the unfolded protein response (UPR) in primary human atrial fibroblasts (hATF). Thus we tested the degree to which coordination exists between signaling from mitochondria, endoplasmic reticulum and lysosomes during response to simvastatin exposure. Pharmacologic blockade of the activation of ER-dependent cysteine-dependent aspartate-directed protease (caspase)-4 and lysosomal cathepsin-B and -L significantly decreased simvastatin-induced cell death. Simvastatin altered total abundance and the mitochondrial fraction of proapoptotic and antiapoptotic proteins, while c-Jun N-terminal kinase/stress-activated protein kinase mediated effects on B-cell lymphoma 2 expression. Chemical inhibition of autophagy flux with bafilomycin-A1 augmented simvastatin-induced caspase activation, UPR and cell death. In mouse embryonic fibroblasts that are deficient in autophagy protein 5 and refractory to autophagy induction, caspase-7 and UPR were hyper-induced upon treatment with simvastatin. These data demonstrate that mevalonate cascade inhibition-induced death of hATF manifests from a complex mechanism involving co-regulation of apoptosis, autophagy and UPR. Furthermore, autophagy has a crucial role in determining the extent of ER stress, UPR and permissiveness of hATF to cell death induced by statins.