Inflammatory processes, cells involved

IFN- 3 reduces the induction by inflammatory cytokines of adhesion molecules and of MHC class I and II complex on endothelial cells, a process preceding attachment and transendothelial migration of T-cells. These anti-inflammatory effects of IFN- 3 exemplify antagonistic actions of type I and type IIIFN. There is, indeed, much clinical evidence for the involvement of IFN-y in inflammatory processes - through activation of iNOS and subsequent secretion of NO - leading to the establishment of autoimmune diseases as for instance in rheumatoid arthritis. 

As with UC, the immune activation seen in CD involves the release of many proinflammatory cytokines. Cytokines thought to play major roles in CD are derived from T-helper type 1 cells and include interferon-y, TNF-a, and IL-1, IL-6, and IL-12. TNF-a is a major contributor to the inflammatory process seen in CD. Its physiologic effects include activation of macrophages, procoagulant effects in the vascular endothelium, and increases in production of matrix metallo-proteinases in mucosal cells.9,15 Excessive production of both... 

Corticosteroids have potent anti-inflammatory properties and are used in active IBD to rapidly suppress inflammation. Corticosteroids have favorable effects in modulating several cell types involved in the inflammatory process.20,21 They may be administered systemically or delivered locally to the site of action by altering the drug formulation (Table 16-2). Because these drugs usually improve symptoms and disease severity rapidly, they should be restricted to short-term management of active disease. Long-term use of systemic corticosteroids is... 

Deposition of urate crystals in synovial fluid results in an inflammatory process involving chemical mediators that cause vasodilation, increased vascular permeability, complement activation, and chemotactic activity for polymorphonuclear leukocytes. Phagocytosis of urate crystals by leukocytes results in rapid lysis of cells and a discharge of proteolytic enzymes into the cytoplasm. The ensuing inflammatory reaction is associated with intense joint pain, erythema, warmth, and swelling. 

N-formyl-peptides (FP) are G-protein coupled receptors and members of the phagocyte chemotactic receptor family, which are involved in inflammatory processes. N-formyl-peptides are indicators of the presence of bacteria or damage to host cells in mitochondria. Receptor binding is giving a signal for infection... 

TNF-a is a cytokine produced by T cells and mast cells. TNF-a is involved in the gut inflammatory process in Crohn disease, where treatment with soluble TNF-a receptor and anti-TNF-a antibodies and soluble TNF-a receptor has the highest... 

The third type of response to injury, which falls under the general heading of inflammation (suffix itis ), manifests itself in several complex ways. It involves extracellular processes and cells of the immune system. Inflammation is often part of the road to repair from injury, but the inflammatory process can, if extensive, be highly damaging. Inflammation can be acute or chronic in nature. Repair can occur by regeneration of cells, for example by enhanced growth of adjacent cells or it can occur by a process called fibrosis. Some examples of inflammatory responses and repair are brought out in Chapter 4. 

Aspirin has been used to treat arthritis for approximately 100 years, but its mechanism of action—inhibition of COX activity—was not discovered until 1971. COX-2 appears to be the form of the enzyme most associated with cells involved in the inflammatory process although, as outlined above, COX-1 also contributes significantly to prostaglandin biosynthesis during inflammation. 

In primary cultures of neonatal cerebellar granule neurons, all Ca2+ sensors, calmodulin, protein kinases C (PKC), and the p21(ras)/phosphatidylinositol 3 -kinase (Ptdlns-3K)/Akt pathway, converge towards NF-kB at the levels of nuclear translocation as well as transcription. The duration of NF-kB activation is a critical determinant for sensitivity toward excitotoxic stress and is dependent on the different upstream and downstream signaling associated with various kinases. This is in contrast to studies in non-neuronal cells, which either do not respond to Ca2+ or do not simultaneously activate all three cascades (Lilienbaum and Israel, 2003). Collective evidence suggests that brain inflammatory processes differ from systemic inflammation not only in the involvement of various types of neural cells but also in differences in response to second messengers. 

The transfection data summarized in Fig. 13 were obtained with primary human umbilical artery endothelial cells (HUAEC). Vascular endothelial cells, acting as an interface between circulating blood and tissues, are known to be involved in inflammatory processes, in atherosclerosis and angiogenesis, and represent a remarkable challenge as a gene therapy target. Their therapy with nonviral vectors... 

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