7 cells were pre-treated for 4
hours with GTA+ve or GTA-ve extracts followed by the addition of LPS (1 ug/ml) for 20 hours. (A) TNFα mRNA transcripts as determined by real-time rtPCR, (B) TNFα relative protein levels in cell lysates following 80 ug/ml treatment, and (C) TNFα protein levels in conditioned media as determined by ELISA. Asterisks indicate p < 0.05 relative to LPS treatment alone. Data are expressed as the ACP-196 in vivo average of three duplicate experiments ± 1S.D. Dabrafenib mouse Figure 8 COX2 and IL-1β response in RAW264.7 cells treated with GTA+ve and GTA-ve extracts. RAW264.7 cells were pre-treated for 4 hours with GTA+ve or GTA-ve extracts followed by the addition of LPS (1 ug/ml) for 20 hours. (A) COX2 and (B) IL-1β mRNA levels were determined by real-time rtPCR. (C) IL-1β levels following 80 ug/ml treatment in cell lysates as determined by ELISA. Asterisks indicate p < 0.05 relative to LPS treatment alone. Data are expressed as the
average of three duplicate experiments ± 1S.D. Discussion this website The regulation of inflammation and the ability to control cell growth are two processes intricately linked with cancer. When acute inflammatory processes are not resolved by the appropriate enzymatic conversion of fatty acid mediators into specific oxygenated products [1, 20, 21], a state of chronic inflammation can ensue, which can further lead to sporadic DNA mutations, the activation of pro-oncogenic pathways and ultimately cancer (for example see
). When such detriments occur, they normally trigger a cascade of intracellular events leading to the induction of apoptotic-mediated cell death. Thus it is the fine control between inflammatory and apoptotic processes, likely early in life, which might be a key determinant of one’s risk of subsequent cancer development. Based on the tumor-independent reduction of GTAs previously reported in CRC patient serum , their age-related reduction in the general population , and their structural resemblance to the inflammation-resolving protectins and resolvins, we hypothesized that GTAs might represent a novel endogenous cancer-protective ADAMTS5 metabolic system. Although we focused specifically on a subset of 28-carbon GTAs, the GTA family comprises a large number of structurally related novel hydroxylated polyunsaturated ultra long-chain fatty acids ranging in size between 446 and 596 Da and containing up to 36 carbons . In studies completed to date, GTAs appear to represent a human-specific metabolic system as they have only been detected in human serum (or plasma) and not in the serum or plasma of other mammals including mice, rats, cows, dogs, and rabbits. Likewise, GTAs are absent from several types of plant-based products such as grains and seed oils, as well as human tissues including colonic tumors and normal colon epithelium (unpublished observations).