Anti-CCL13 polyclonal antibody [Biotin]

Background: Regular aspirin use may decrease cancer risk by reducing chronic inflammation. However, associations between aspirin use and circulating markers of inflammation have not been well studied. Methods: Serum levels of 78 inflammatory markers were measured in 1,819 55-to 74-year-old men and women in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Data were combined from three completed case-control studies and reweighted to the PLCO screening arm. Self-reported aspirin and ibuprofen use (number of tablets taken per day/week/month) over the previous 12 months was collected at baseline. Associations between (i) nonregular (< 4 tablets/month), (ii) low (1-4 tablets/week), (iii) moderate (1 tablet/day), or (iv) high (2+tablets/day) regular aspirin or ibuprofen use and marker levels were assessed with weighted logistic regression. Results: Aspirin use was nominally associated with (P-trend across categories <= 0.05) decreased levels of chemokine C-C motif ligand 15 [CCL15; OR, 0.5; 95% confidence intervals (CI), 0.3-0.8; moderate versus nonregular use]; soluble vascular endothelial growth factor receptor 2 (sVEGFR2; OR, 0.7; 95% CI, 0.4-1.0); soluble tumor necrosis factor receptor 1 (sTNFR1; OR, 0.6; 95% CI, 0.4-0.9) and increased levels of CCL13 (OR, 1.3; 95% CI, 0.8-2.1); CCL17 (OR, 1.1; 95% CI, 0.7-1.9) and interleukin 4 (IL4; OR, 1.6; 95% CI, 0.9-2.8). Trends were not statistically significant following correction for multiple comparisons. Likewise, no statistically significant associations were observed between ibuprofen use and marker levels. Conclusions: No significant associations were observed between regular aspirin use and the inflammatory markers assessed. Impact: Additional studies are needed to better understand the relationship between aspirin use, chronic inflammation, and cancer risk. (C) 2015 AACR.

The chemokine receptor CCR2, which has been implicated in a variety of inflammatory, autoimmune, and cardiovascular conditions, binds several natural chemokine ligands. Here, we assessed the recruitment of beta-arrestin to CCR2 in response to these ligands using bioluminescence resonance energy transfer technology. Compared with CCL2, which was considered as a full agonist, other CCR2 ligands were partial agonists with reduced efficacy and potency. Agonist potencies were not a function of their affinity for CCR2. Efficacy of arrestin recruitment matched that of agonist-induced CCR2 internalization. Although the potency and efficacy rank orders of the ligands in arrestin recruitment were similar to those observed for G alpha(i1) activation, arrestin recruitment was at least in part resistant to G alpha(i/o)-inactivating pertussis toxin, suggesting partial independence from G alpha(i/o). The degree of pertussis toxin resistance of arrestin recruitment was different between the chemokines. Moreover, qualitative differences between the arrestin responses to the different ligands were identified in the stability of the response: although CCL7-induced arrestin recruitment had a half-life of less than 15 min, CCL8 and CCL13 induced stable CCR2-arrestin interactions. Finally, the ligands stabilized different conformations of the CCR2 homodimer. Our results support the validity of models for receptor-ligand interactions in which different ligands stabilize different receptor conformations also for endogenous receptor ligands, with corresponding implications for drug development targeting CCR2.