Inflammatory bowel disease chemokines

Mazzucchelli L> Hauser C, Zgraggen K, et al. Differential in situ expression of the genes encoding the chemokines MCP-1 and RANTES in human inflammatory bowel disease. J Pathol 1996 178 201-6. 

Tea and its constituents have been shown to be effective against inflammatory bowel disease by inhibiting the expression of inflammatory genes such as TNFa, IFNy, iNOS, and NE-kB, thereby reducing the production of associated inflammatory mediators. EGCG has also been shown to be effective in inhibiting the production of chemokines (IL-8) and PGE2 in rat colonic cells. ... 

This chapter discusses the role of chemokines and their receptors in inflammatory diseases of the airways (asthma and COPD), the intestinal tract (inflammatory bowel diseases), the joints (arthritis), the blood vessels (arteriosclerosis), the central nervous system (multiple sclerosis) and the skin (psoriasis). Investigations of receptor-mediated and intracellular signal pathways in chemokine—receptor interactions... 

Chemokine and Inflammatory Bowel Diseases 121 Table 6.5 Chemokine receptors and their ligands demonstrated to be involved in asthma. 

Table 6.6 Chemokines and chemokine receptors and target cells demonstrated to be involved in inflammatory bowel disease.

In conclusion, the mentioned studies suggest that proinflammatory chemokines can either sensitize or desensitize receptor functions on or directly activate peripheral NANC nerves. This cross-(de)sensitization between neuronal (anti)pain and chemokine receptors or direct activation of NANC nerves may contribute to the development of visceral pain observed in inflammatory bowel disease and irritable bowel syndrome. 

Gijsbers, K., Van Assche, G., Joossens, S., Struyf, S., Proost, P., Rutgeerts, P., Geboes, K., and Van Damme, J. (2004). CXCRl-binding chemokines in inflammatory bowel diseases Down-regulated IL-8/CXCL8 production by leukocytes in Crohn s disease and selective GCP-2/CXCL6 expression in inflamed intestinal tissue. Eur. J. Immunol. 34, 1992-2000. 

Z Graggen, K., Walz, A., Mazzucchelli, L., Stricter, R. M., and Mueller, C. (1997). The C-X-C chemokine ENA-78 is preferentially expressed in intestinal epithelium in inflammatory bowel disease. Gastroenterology 113, 808-816. 

Inflammation is considered the key feature of the immune system response to injury. The main symptoms of inflammations are redness, swelling, pain, and heat. The body s immime system commonly controls the inflammation itself When the inflammations become imcon-trollable, the body becomes diseased, leading to chronic discomfort [109]. This chronic inflammation is the major component of various chronic diseases, including inflammatory bowel disease, rheiunatoid arthritis, osteoporosis, and allergies [110,111]. Along with activation and proliferation of inflammatory cells, cytokines and chemokines are produced in excessive quantities in chronic inflammatory diseases. The primary targets of the anti-inflammatory compounds are the inhibition of inflammatory cell recruitment and proinflammatory mediator production [112]. 

Difluorophenyl)methyl]thio -7- [(1 S,2S)-2-hydroxy-l-(hydroxymethyl)propyl] amino thiazolo [4,5 -d]pyrimidin-2(3H)-one 126 (Seheme 56) which are useful for treating a chemokine mediated diseases sueh as asthma, allergic rhinitis, COPD, inflammatory bowel disease, osteoarthritis, osteoporosis, rheumatoid arthritis, psoriasis, cancer, etc., was prepared in a 7-step process, starting from 4-amino-6-hydroxy-2-mercaptopyrimidine and 2,3-difluorobenzyl bromide [82],... 

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. 

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