Lipoxin A yields an electrophilic 15-oxo metabolite that mediates FPR2 receptor-independent anti-inflammatory signaling.

The enzymatic oxidation of arachidonic acid is proposed to yield trihydroxytetraene species (termed lipoxins) that resolve inflammation via ligand activation of the formyl peptide receptor, FPR2. While cell and murine models activate signaling responses to synthetic lipoxins, primarily lipoxin A (LXA), there are expanding concerns about the reported biological formation, detection, and signaling mechanisms ascribed to LXA and related di- and tri-hydroxy ω-6 and ω-3 fatty acids. The generation and signaling actions of LXA and its primary 15-oxo metabolite were assessed in control, lipopolysaccharide-activated, and arachidonic acid-supplemented RAW264.

Phenotypic and genotypic association of epithelial IL1RL1 to human TH2-like asthma.

Background: Severe asthma remains poorly characterized, although it likely consists of at least 1 phenotype with features of TH2-like inflammation. IL1RL1, encoding both the IL-33 receptor, ST2L, and decoy receptor, sST2, has been genetically associated with asthma, though the mechanism for susceptibility remains unknown.

Objective: Given previous data supporting a role for IL1RL1 in TH2 inflammation, we hypothesized that ST2L expression might be increased in TH2-like asthma and that expression levels would be associated with single nucleotide polymorphisms in IL1RL1, possibly explaining its genetic relationship with asthma.

Prostaglandin D₂ pathway upregulation: relation to asthma severity, control, and TH2 inflammation.

Background: Bronchoalveolar lavage (BAL) fluid prostaglandin D₂(PGD₂) levels are increased in patients with severe, poorly controlled asthma in association with epithelial mast cells (MCs). PGD₂, which is generated by hematopoietic prostaglandin D synthase (HPGDS), acts on 3 G protein-coupled receptors, including chemoattractant receptor-homologous molecule expressed on TH2 lymphocytes (CRTH2) and PGD₂ receptor 1 (DP1). However, much remains to be understood regarding the presence and activation of these pathway elements in asthmatic patients.