IL 12 plays overnight delivery a critical role in the early inflammatory response to infection. An increased pro duction of IL 12 is involved in the pathogenesis of a number of autoimmune inflammatory diseases. IL 12 consists of two subunits which are linked together by a disulfide bond to give heterodimeric p70 molecule. We showed that brain pericytes release substantial amounts of both the heterodimeric p70 molecule and p40 subunits after LPS stimulation. Release of the p40 subunit was higher than release of the heterodimeric p70 molecule itself. Interestingly, the p40 subunit of IL12 can link together and this homodimeric form has been shown to increase expression of leukocyte chemoattractant factor in microglia. IL 9 is another pleiotropic cytokine whose production was markedly increased after LPS stimulation Inhibitors,Modulators,Libraries of brain pericytes.

Inhibitors,Modulators,Libraries IL 9 is mainly produced by T lymphocytes and mediates allergic inflammation in tissues such as the lung and intestine. In the CNS, the IL 9 recep tor complex is present on astrocytes and IL 9 stimulated astrocytes express CCL 20 chemokine which promotes infiltration of Th17 cells into the CNS. IL 13 is known as an anti inflammatory cytokine that is produced by microglia but not astrocytes or neurons after direct injection of LPS into the cortex. Neurons Inhibitors,Modulators,Libraries are required for IL 13 production by microglia and pro duction of IL 13 by microglia leads to the death of acti vated microglia and enhancement of neuronal survival. In our study, IL 13 production by brain pericytes was elevated after LPS treatment, this shows that peri cytes are a source of IL 13 as well.

Additionally, compared to published results from LPS treated Inhibitors,Modulators,Libraries mouse microglia, production of IL1 a and TNF alpha, a two typical proinflammatory cytokines, by brain pericytes was low. This shows that although peri cytes and microglia both respond to LPS, the profile of cytokines released is different. Recently an interesting study comparing the gene pro file expression of different cell components of neurovas cular unit in adult or during the development was published. The study revealed several important genes that are involved in pericyte endothelial signaling such as transforming growth factor beta superfamily members bmp5 and nodal. It would be interesting to perform such study with immune challenged neurovascular unit as well. Neurodegenerative processes are closely associated with neuroinflammation.

In Alzheimers disease, increased production and impaired transport lead to accumulation of toxic amyloid beta peptide deposits along the vascular system in patients affected Inhibitors,Modulators,Libraries by this disease. LRP 1 at the brain endothelial cell is an impor tant transporter selleck compound for the brain to blood efflux of amyloid beta peptide and in neurons is important in the processing of amyloid precursor protein.