Inflammation chemokines

Taub DD, Oppenheim JJ. Chemokines, inflammation and the immune system. Ther Immuno 1994 1 229-46. 

Luster, A. D. (1998). Mechanisms of disease Chemokines, chemotactic cytokines that mediate inflammation. N. Engl. J. Med. 338 436-445. 

A number of adipokines are linked to inflammation and immunity (Fig. 1). This includes both leptin and adiponectin, and also a number of other key inflammatory proteins, particularly cytokines and chemokines [1]. The cytokines and chemokines encompass interleukin-1(3 (EL-1 (3), IL-6, DL-10, TNFa, monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor (MIF). Other major inflammation-related adipokines include nerve growth factor (NGF), and acute phase proteins such as serum amyloid A and haptoglobin. In addition, adipocytes secrete plasminogen activator inhibitor-1 (PAI-1), which is an important thrombotic factor as well as an acute phase protein. 

Current evidence suggests that PPAR activation may limit inflammation and hence atherosclerosis. Both PPAR-a and PPAR-y can reduce T-cell activation, as shown by decreased production of EFN-y. PPAR-a agonists also rqness endothelial VCAM-1 expression and inhibit the inflammatory activation of vascular SMCs, while PPAR-y agonists repress endothelial chemokine expression and decrease macrophage MMP production. 

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

A cascade of proteins of the immune response that can be triggered by antigen-antibody complexes and by the innate immune system (e.g. exposure to microbial polysaccharides) to raise the immune response. Complement proteins can detect and bind to foreign material or immune complexes and label them for phagocytosis. They can also cause inflammation by directly degranulating mast cells and releasing chemokines to recruit other immune cells into the affected area. 

Inflammatory disorders are due to hyperactivity of leukocytes and overexpression of their associated integrins, cytokines, and chemokines, which leads to various disorders including arthritis, bowel diseases and other chronic inflammations. 

Polydefkis M, Yiannoutsos CT et al (2002) Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy. Neurology 58(1) 115-119 Power C, Gill MJ et al (2002) Progress in clinical neurosciences The neuropathogenesis of HIV infection host-virus interaction and the impact of therapy. Can J Neurol Sci 29(l) 19-32 Premack BA, SchaU TJ (1996) Chemokine receptors gateways to inflammation and infection. Nat Med 2(11) 1174-1178... 

White FA, Bhangoo SK et al (2005a) Chemokines integrators of pain and inflammation. Nat Rev Drug Discov 4(10) 834-844... 

Cartier L, Hartley O, Dubois-Dauphin M, Krause KH (2005) Chemokine receptors in the central nervous system role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 48 16-42... 

Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354 610-621... 

Belmadani A, Tran PB, Ren D, Miller RJ (2006) Chemokines regulate the migration of neural progenitors to sites of neuroinflammation. J Neurosci 26 3182-3191 Bensinger SJ, Tontonoz P (2008) Integration of metabolism and inflammation by lipid activated nuclear receptors. Nature 454 470-477... 

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