Inflammatory signals

It is accepted that oxidation of LDL is a key event in endothelial injury and dysfunction. Oxidised LDL (oxLDL) may directly injure the endothelium and trigger the expression of migration and adhesion molecules. Monocytes and lymphocytes interact with oxLDL and the phagocytosis which follows leads to the formation of foam cells, which in turn are associated with the alteration of the expression pattern of growth regulatory molecules, cytokines and pro-inflammatory signals. The proposed role of oxLDL in atherogenesis, based on studies in vitro, is shown in Fig. 2.1. 

Oestvang, J. and Johansen, B. (2006). PhospholipaseA(2) A key regulator of inflammatory signalling and a connector to fibrosis development in atherosclerosis. Biochim. Biophys. Acta - Mol. Cell Biol. Lipids 1761, 1309-1316. 

The activity of p38/SAPK is central to the genetic changes that occur in response to cytokine activated pro-inflammatory signaling in astrocytes and microglia. p38/SAPK... 

In a related study, resveratrol significantly reduced colonic injury, neutrophil infiltration, and drastically reduced the PGD2 concentration by inhibiting COX-2, but not affecting COX-1 [Martin et al., 2004]. It appears that the antiinflammatory activity of resveratrol may be realized through the inhibition of both COX-1 and COX-2-mediated pro-inflammatory signaling, suppression of pro-inflammatory mediator production, as well as from its potent antioxidative effects. 

Figure 15.3 Resveratrol modulation of pro-inflammatory signaling pathways. Resver-atrol represses transcriptional activation of various pro-inflammatory genes by inhibiting pro-inflammatory stimuli-induced activation of upstream kinases, such as MAP kinases, PI3K/Akt, IKK, PKC, etc., and blocking the DNA binding of eukaryotic transcription factors, such as NF-kB, AP-1, and STAT3.

Kundu JK, Shin YK, Surh Y-J. 2006b. Resveratrol modulates phorbol ester-induced pro-inflammatory signal transduction pathways in mouse skin in vivo NF-kappaB and AP-1 as prime targets. Biochem Pharmacol 72 1506-1515. 

Colangelo V., Schurr J., Ball M. J., Pelaez R. P., BazanN. G., and Lukiw W. J. (2002). Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1 Transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J. Neurosci. Res. 70 462 173. 

The more we learn about the function of sensory neurons and their receptors and signaling mechanisms, the more it becomes clear that sensory neurons are not only passive mediators of painful or inflammatory signals. Recently it has been shown that sensory neurons play an active role in the inflammatory process in... 

Rao, N., Nguyen, S., Ngo, K., Fung-Leung, W.P. A novel splice variant of interleukin-1 receptor (IL-lR)-associated kinase 1 plays a negative regulatory role in Toll/IL-lR-induced inflammatory signaling. Mol Cell Biol 25 (2005) 6521-6532. 

Structural studies have revealed that several other domains involved in cell death and inflammatory signaling transduction, including the death effector domain (DED) (Fig. 11C), the caspase recruitment domain (CARD) and the Pyrin domain (PYD), also possess the same six helix bundle structures of DDs (Chou et al, 1998 Eberstadt et al, 1998 Hiller et al, 2003), forming the death domain superfamily. Interestingly, interactions have only been observed among proteins within the same subfamilies with no cross interactions between proteins from different subfamilies. 

As the CNS representatives of the monocytic cell lineage, microglia undergo an inflammatory type of activation in response to brain injury and stress. Among the products of microglia activated by inflammatory signals is nitric oxide, which is produced by the exquisitely NF-KB-sensitive, inducible nitric oxide synthase. This enzyme can be elevated in an NF-xB-dependent manner in astrocytes (Akama et al.,... 

Lee JH, Park EJ, Kim OS, Kim HY, Joe E-H, Jou I (2005) Double-stranded RNA-activated protein kinase is required for the LPS-induced activation of STATl inflammatory signaling in rat brain glial cells. GLIA 50 66-76... 

Herber DL, Mercer M, Roth LM, Symmonds K, Maloney J, Wilson N (2007) Microglial activation is required for Abeta clearance after intracranial injection of Upopolysaccharide in APP transgenic mice. J Neuroimmune Pharmacol 2 222-231 Hide T, Takezaki T, Nakamura H, Kuratsu J, Kondo T (2008) Brain tumor stem cells as research and treatment targets. Brain Tumor Pathol 25 67-72 Hill JM, Zhao Y, Qement C, Neumann DM, Lukiw WJ (2009) HSV-1 infection of human brain cells induces miRNA-146a and Alzheimer-type inflammatory signaling. Neuroreport 20 1500-1505... 

Cyclopentenone IsoPs also exert biological effects in non-neural tissue. Recent studies employing macrophages reveal that 15-A2-IsoPs potently suppress lipopolysacharide (LPS)-induced inflammatory signaling via inhibition of the... 

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