Diverging Mechanisms of Activation of Chemokine Receptors Revealed by Novel Chemokine Agonists

CXCL8/interleukin-8 is a pro-inflammatory chemokine that triggers pleiotropic responses, including inflammation, angiogenesis, wound healing and tumorigenesis. We engineered the first selective CXCR1 agonists on the basis of residue substitutions in the conserved ELR triad and CXC motif of CXCL8. Our data reveal that the molecular mechanisms of activation of CXCR1 and CXCR2 are distinct: the N-loop of CXCL8 is the major determinant for CXCR1 activation, whereas the N-terminus of CXCL8 (ELR and CXC) is essential for CXCR2 activation. We also found that activation of CXCR1 cross-desensitized CXCR2 responses in human neutrophils co-expressing both receptors, indicating that these novel CXCR1 agonists represent a new class of anti-inflammatory agents. Further, these selective CXCR1 agonists will aid at elucidating the functional significance of CXCR1 in vivo under pathophysiological conditions

Combined effects of nitrogen addition and organic matter manipulation on soil respiration in a Chinese pine forest

The response of soil respiration (Rs) to nitrogen (N) addition is one of the uncertainties in modelling ecosystem carbon (C). We reported on a long-term nitrogen (N) addition experiment using urea (CO(NH2)(2)) fertilizer in which Rs was continuously measured after N addition during the growing season in a Chinese pine forest. Four levels of N addition, i.e. no added N (N0: 0 g N m(-2) year(-1)), low-N (N1: 5 g N m(-2) year(-1)), medium-N (N2: 10 g N m(-2) year(-1)), and high-N (N3: 15 g N m(-2) year(-1)), and three organic matter treatments, i.e. both aboveground litter and belowground root removal (LRE), only aboveground litter removal (LE), and intact soil (CK), were examined. The Rs was measured continuously for 3 days following each N addition application and was measured approximately 3-5 times during the rest of each month from July to October 2012. N addition inhibited microbial heterotrophic respiration by suppressing soil microbial biomass, but stimulated root respiration and CO2 release from litter decomposition by increasing either root biomass or microbial biomass. When litter and/or root were removed, the "priming" effect of N addition on the Rs disappeared more quickly than intact soil. This is likely to provide a point of view for why Rs varies so much in response to exogenous N and also has implications for future determination of sampling interval of Rs measurement