Some Chlamydia infected host cells are resistant selleck chem inhibitor to pro apop totic stimuli such as TNF , Fas antibody, staurosporine, Inhibitors,Modulators,Libraries and UV light, and C. pneumoniae infection has been shown to down regulate pro apoptotic cytoplasmic pro teins such as caspase 3 and cytochrome c. Intriguingly, C. pneumoniae infection also has been shown to activate anti apoptotic proteins such as Bcl 2 and NF , the latter of which is critical in the expression of multiple genes involved in inflammatory responses and anti apoptotic mechanisms. Our laboratory has demonstrated C. pneumoniae infection in brain tissues from patients diagnosed with AD. Many cell types including monocytes, endothelial cells, glial cells and neurons were shown to be infected.

Interest ingly, the infected cells did not appear to be undergoing degenerative changes, even though they were in the vicin Inhibitors,Modulators,Libraries ity of cells demonstrating neurodegenerative pathology characteristic of AD. C. pneumoniae also has Inhibitors,Modulators,Libraries been identi fied within neurons in the AD brain by in situ hybridiza tion as well as in the Inhibitors,Modulators,Libraries olfactory neuroepithelia, the olfactory bulbs and endothelia from C. pneumoniae infected BALB c mice by immunohistochemistry. Collectively, these studies have correlated infection with C. pneumoniae to the neuropathology characteristic of AD, but the specific influences of infection on neuronal cell injury, cell death, and chronic inflammation are still being determined. A major factor in AD is an inflammatory process thought to be stimulated by the processing and deposition of amyloid. Although amyloid may promote inflammation, infectious agents such as C.

pneumoniae also could provoke neuroinflammation in sporadic, late onset AD that precedes or coincides with the deposition of A 1 42 in the AD Inhibitors,Modulators,Libraries brain. The exact role that chlamydial infection plays with respect to abnormal processing and deposition of amyloid, however, remains to be deter mined and is beyond the scope of this report. In contrast, the focus of the current study was to determine how C. pneumoniae infection influences the apoptotic process within neuronal cells in culture during both short and long term infections. Results Several experimental paradigms were utilized in these studies to deter mine the relationship between C. pneumoniae infection and apoptosis in neuronal EPZ-5676 mll cells as it relates to the patho genesis of AD. C. pneumoniae was identified within neu rons in hippocampal AD brain tissues. Alzheimer diseased brain tissue from the hippocampal region Immunolabeling using antibodies specific to C. pneumo niae revealed a punctate labeling pattern identifying the chlamydial bodies within several neurons.