Differential accumulation levels in the brain of rats exposed to the endocrine disruptor 4-tert-octylphenol (OP).

Octylphenol (OP) is an endocrine-disrupting chemical that accumulates in various organs. It has also been shown to exert noxious effects on the central nervous system. In the present study, we measured in Sprague-Dawley rats the degree of OP accumulation in different areas of the brain and investigated the effect of OP in pain modulation. Two groups of male Sprague-Dawley rats were treated for 20 days with 50mg/kg BW/day of OP (group 1) or vehicle (group 2). At the end of the treatment, the formalin test was performed to evaluate the effect of OP exposure on pain. Soon after, rats were sacrificed, and the accumulation of OP in the cerebral cortex, hippocampus, hypothalamus, cerebellum, thalamus, striatum, mesencephalus and ventral hindbrain was measured by HPLC analysis. The results showed a greater accumulation of OP in the cerebral cortex compared to all the other areas; there was also more accumulation in the cerebellum compared to the mesencephalus and thalamus. No accumulation was found in the striatum. These results suggest that there is a preferential accumulation of OP in different areas of the brain with consequences to neural behaviour. On the contrary, experiments on facial grooming did not show significant effects of OP on pain.

Th1-Th2 response in hyperprolactinemic mice infected with Salmonella enterica serovar Typhimurium.

Prolactin (PRL) is a pituitary hormone and a cytokine known to regulate several physiological functions. It plays a role in modulating the immune system of rodents and humans. A hormonal protection against listeria and salmonella infections has been previously ascribed to effects of PRL on immunocompetent cells. Here, the role of PRL in the Th1-Th2 response was evaluated based on the pattern of cytokines release by splenocytes from hyperprolactinemic mice infected with Salmonella enterica serovar Typhimurium. Hyperprolactinemia by pituitary graft reduced the number of bacteria in spleens of in vivo infected mice. Modulation of Th1 (IFN-gamma, IL-12) and Th2 (IL-4, IL-10) cytokine production by splenic cells was found. Our results indicate that PRL can up-regulate IFN-c and IL-12 secretion in response to salmonella infection, confirming its in vivo immunostimulatory effect and suggesting hormonal participation in the genesis and sustenance of the Th1 response.

Porins and lipopolysaccharide from Salmonella typhimurium regulate the expression of CD80 and CD86 molecules on B cells and macrophages but not CD28 and CD152 on T cells.

OBJECTIVE: The aim of this study was to evaluate the effect of porins from Salmonella typhimurium on costimulatory molecules such as CD80/CD86 and CD28/CD152. The interactions between these molecules are able to influence the immune response through the regulation of cytokines release which, on their own, are able to regulate the immunological response by a feedback mechanism. METHODS: S. typhimurium strain SH5014 (a rough lipopolysaccharide (LPS) producing strain) was used as the source of porins and LPS. Peripheral blood mononuclear cells were obtained from healthy adult donors. THP1 cells were obtained from ATCC (Rockville, MD, USA). Immunofluorescence and flow cytometry were performed using a FACS IV (Becton-Dickinson, Mountain View, CA, USA). RESULTS: Our results show that porins of S. typhimurium increase the expression of CD86 and the expression of CD80 both on B lymphocytes and macrophages, while the expression of CD28 and CD152 on T lymphocytes was unaltered. The expression of CD80 and CD86 is dose-dependent and starts after 24 h post treatment, peaks at 48 h and goes back to the basal value after 72 h. CONCLUSIONS: S. typhimurium porins are able to induce a high expression of costimulatory molecules (CD80 and CD86) on lymphocytes and macrophages.

Chlamydia pneumoniae infections prevent the programmed cell death on THP-1 cell line.

Chlamydia pneumoniae is an obligate intracellular bacterium which frequently causes airway infection in humans and has been implicated in chronic inflammatory disease and atherosclerosis. Here we show that infection with C. pneumoniae protects THP-1 cells against the apoptosis which spontaneously occurs in macrophages in the absence of an activation signal. Analysis by flow cytometry at different post-infection times revealed that 50+/-7% of THP-1 cells were apoptotic at 48 h after onset of the experiments, whereas C. pneumoniae-infected cultures (multiplicity of infection, MOI=30) displayed only 18+/-4% of cells in apoptosis. At MOI=20 and MOI=10 the cells susceptible to apoptosis at 48 h were 28+/-5% and 35+/-6% respectively. Moreover, the results show that heat-inactivated bacteria do not give significant protection against apoptosis, even at higher MOI (MOI=30), while UV-treated Chlamydia did provide a degree of protection against apoptosis. These data suggest that the anti-apoptotic effect of C. pneumoniae requires a heat-labile component released during infection, and that the effect is not lipopolysaccharide-dependent.