On the other hand, the Chlamydia protein associating with death domains is involved in caspase dependent apoptosis. Cas pase independent cell death is obviously triggered by apoptosis selleckchem inducing factor. Whichever control mechanisms occur, it shows Chlamydia to have evolved a highly dynamic regulatory strategy for apoptosis preven tion. In our system, aponecrotic HAEC displayed a con densed chromatin but no signs of nuclear fragmentation. Such a different DNA cleavage pattern, compared to apop totic nuclei, was also described in other studies performed with Chlamydia trachomatis and C. pneumoniae. Since aponecrotic HAEC contained prior inclusions, it is probable that the apoptotic process was interfered by Chlamydia residing in inclusions.

Hence, the interrupted apoptotic cascade together Inhibitors,Modulators,Libraries with the release of the bacteria might cause this particular form of chimeric cell death. Moreover, Inhibitors,Modulators,Libraries aponecrotic cell death was accompanied by a release of the pro inflammatory HMGB1 protein. HMGB1 is a multifunctional protein which on one hand binds and modifies DNA structure to facilitate transcription, replica tion Inhibitors,Modulators,Libraries and repair and on the other hand acts as a pro inflammatory cytokine in the extra cellular milieu. HMGB1 released from damaged endothelium may con tribute to inflammatory responses in atherosclerotic lesions. It has been reported that addition of HMGB1 induces expression of leukocyte adhesion molecules such as vascular cell adhesion molecule and the release of tumour necrosis factor from cultured microvascular endothelial cells.

Up regulation of another adhesion molecule, namely intracellular cell adhesion molecule, was observed in human umbilical vein endothelial cells upon Chlamydia infection. However, HMGB1 also acts as a strong chemotactic agent for smooth muscle cells. Thus, a damaged endothelium might induce the migration of SMC into the intima, another crucial factor in the progression of athero Inhibitors,Modulators,Libraries sclerosis. These numerous observations indicate that HMGB1 released from C. pneumoniae infected HAEC may be a possible mediator and enhancer of local inflamma tion and progression of atherosclerosis. A further strong pro inflammatory factor that might trig ger inflammation in atherosclerotic lesions is cHsp60. We indeed found cHsp60 predominantly in inclusions and scattered in aponecrotic HAEC.

Beside their function as a chaperones, bacterial Hsp60 are known to be highly immunogenic Inhibitors,Modulators,Libraries and are able to activate the immune response. It has been shown that cHsp60 regulates macrophage tumour necrosis factor and matrix metalloproteinase expression and secretion which in turn could enhance the immune response and destabilize the atherosclerotic lesion. It has been additionally Cisplatin DNA Synthesis reported that immune cells not only interact with bacterial Hsp60 but also with endogenous Hsp60 expressed by stressed endothelial cells. Conclusively, C.