Lactobacilli are commensal Gram positive bacteria that widely populate the healthy female vaginal mucosa. Several Lactobacillus strains have been implicated http://www.selleckchem.com/products/Bosutinib.html by epidemiologic and or experimental evi dence in the maintenance of a homeostatic infection free microenvironment most notably due to the impact of the bacterias lactic acid and H2O2 production Inhibitors,Modulators,Libraries in gen erating an adverse environment for HIV and other STDs. These properties may contribute to the re duction of viral particles at the site of infection. In contrast, a reduction in the number of Lactobacillus in the vaginal microbiota has been associated with the acquisition of bacterial vaginosis. The presence of BV is correlated with an increased risk of ac quiring herpes simplex virus type 2, HIV and other STDs.
In turn, co infection with sexually trans mitted pathogens is associated with an increased risk of acquiring and transmitting HIV. Naturally occur ring lactobacilli demonstrate an inverse relationship with HIV infectivity. Sha et al. found an inverse ratio between indigenous Lactobacillus counts and HIV RNA detected in cervical vaginal Inhibitors,Modulators,Libraries lavage at nearly significant levels. Inhibitors,Modulators,Libraries In another study, L. jensenii demonstrated a reduction in HIV infection by 23% in vitro. Our finding that L. jensenii can induce NFB activa tion and at the same time maintain low levels of inflammation associated proteins has important implica tions for its potential use as a vaginal probiotic or biotherapeutic. NFB is a major transcription factor that plays a key role in inflammatory disease and upre gulates a myriad of inflammation associated genes in cluding those studied here.
At the same time NFB participates in its Inhibitors,Modulators,Libraries own negative feedback loop promoting the resolution of inflammation in vivo. Thus, the net effect of NFB activation depends on the cell and tissue context, the interplay of a number of intra and extra Inhibitors,Modulators,Libraries cellular factors, and the nature of the activating signal. It has been previously shown that some lactoba cillus species can cause NFB activation and yet maintain low levels of IL 8 and RANTES. Another study showed that L. jensenii can suppress IL 8 induced by TLR ligands. Interest ingly, a non vaginal lactobacillus species induced production of MIP 3 and other vaginal bacteria, associated with bacterial vaginosis e. g. P. bivia and A. vaginae induced simultaneous NFB ac tivation and upregulation of inflammatory proteins in contrast to vaginal L. crispatus and L. acidophilus, which maintained low levels of proinflammatory proteins in the vaginal colonization context. We now demon strate for the first time using an expanded panel of innate immunity mediators that this immuno modulatory phenomenon is also true for the L. jensenii isolate 1153 and Lenalidomide its bioengineered derivatives.