COX-2 expression

Moreover, COX-2 expression seems to be regulated by synaptic activity [36]. Recently, COX-3 was characterized as generated from COX-1 intron-1 retention [37]. COX-3 is expressed in brain [37], brain microvasculature [38] and has been proposed to be a target of the analgesic/ antipyretic acetaminophen [37,39]. 

COXs thus catalyze the same first committed step of the AA cascade (Fig. 33-2). COX-2, however, is expressed in response to mitogenic and inflammatory stimuli and encoded by an early-response gene. To date we do not understand how COX-3 expression is regulated. In contrast, COX-1 expression is not subject to short-term regulation. Neurons in the hippocampus, as well as in a few other brain regions, are unlike other cells in that they display basal COX-2 expression [36]. This expression is modulated by synaptic activity, such as long-term potentiation, and involves the NMDA glutamate receptors [36,40]. 

Cyclooxygenase-2 participates in aberrant synaptic plasticity during epileptogenesis. Neuronal COX-2 expression is also upregulated in experimental epileptogenesis, when aberrant synaptic plasticity is thought to... 

Han, S. S. et al., Arsenic trioxide represses constitutive activation of NF-kappaB and COX-2 expression in human acute myeloid leukemia, HL-60, J. Cell. Biochem., 94, 695, 2005. 

The mechanistic basis of the anti-neoplastic activity of UDCA and the explanation for the significant difference in bioactivity of UDCA compared with DCA despite marked similarity in chemical structure remain unresolved. UDCA administration in healthy volunteers and colorectal adenoma patients has been demonstrated to decrease the proportion of DCA in aqueous phase stool. Therefore, one possible mechanism of the chemopreventative activity of UDCA is reduction of mucosal secondary bile acid exposure. Consistent with this idea, UDCA administration has been demonstrated to reduce the incidence of K-ras mutations and decrease Cox-2 expression in AOM-induced tumors, which is the opposite of the reported effects of DCA in the same model. However, it is clear that exogenous administration of UDCA has direct anti-neoplastic activity on human CRC cells in vitro, either alone or in combination with DCA, including anti-proliferative and anti-apoptotic effects, as well as induction of cell senescence. " ... 

Andrographolide, thus, has different mechanisms of anti-inflammatory activity. It can inhibit the activation of NF-kB, suppress inducible nitric oxide synthase (iNOS) expression, inhibit COX-2 expression in human fibroblast cells and also prevent oxygen radical production by human. The compound is also able to modulate T-cell activation both in vitro as well as in vivo, it is evident that it could prevent initial T-cell priming by interfering with DC maturation and antigen presentation capacity. Therefore, andrographolide may have utility as a therapeutic agent for the treatment of autoimmune diseases, such as multiple sclerosis. " ... 

Levita J, Nawawi A, Mutholib A, Ibrahim S. (2010) Andrographolide inhibits COX-2 expression in human fibroblast cells due to its interaction with arginine and histidine in cylcooxygenase site. J Appl Sci 10 1481-1484. 

Prostaglandins and Cyclooxygenase COX-2 Expression and Cancer Underlying Mechanisms of COX-2 Enzyme and Its Inhibitors on Cancers Effect of COX or Selective COX-2 Inhibitors on Cancer Prevention... 

Primary sites Total number of samples COX-2 expression (%) Ref... 

COX-2 inhibitors may find aplace in colorectal tumor chemoprevention, since they seem to have a better gastrointestinal safety profile than other nonspecific NSAIDs when given to patients for a long time. In addition, this approach for colorectal tumors may be able to be expanded to other COX-2 expressing human tumors. 

Hosomi Y, Yokose T, Hirose Y, et al. Increased cyclooxygenase 2 (COX-2) expression occurs frequently in precursor lesions of human adenocarcinoma of the lung. Lung Cancer 2000 30 73-81. 

There is an additional layer of complexity associated with the effects of renal prostaglandins. In contrast to the medullary enzyme, cortical COX-2 expression is increased by low salt intake, leading to increased renin release. This elevates glomerular filtration rate and contributes to enhanced sodium reabsorption and a rise in blood pressure. PGE2 is thought to stimulate renin release through activation of EP4 or EP2. PGI2 can also stimulate renin release and this may be relevant to maintenance of blood pressure in... 

Lee, S., Kim, H., Chang, ., Baek, J., Park, J., Shin, J., Choi, W., Lee, J., and Paik, W. (2009). DHA and EPA down-regulate COX-2 expression through suppression of NF-kappa activity in LPS-treated human umbilical vein endothelial cells. Korean ]. Physiol. Pharmacol. 13,301-307. 

COX-2 expression is induced during inflammation and is thought to be responsible for the production of eicosanoids... 

COX-2 expression was also found in brain areas related to memory (hippocampus, cortex) in patients with Alzheimer s disease (Ho et al., 1999, Yasojima et al., 1999). These findings together with clinical data suggest new options for the use of COX-2 inhibitors in this indication. 

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