e induction of prostanoid biosynthesis, PGE2 accumulation was accompanied by a parallel increase in 8-iso-PGE2. Thus, 8-iso-PGE2 production Allergy Asthma Immunol Res. 2016 November;8:481-490. http://dx.doi.org/10.4168/aair.2016.8.6.481 http://e-aair.org 487 Sanak 25 20 pg/mL 15 10 5 PGE2 IL-1 Volume 8, Number 6, November 2016 8-iso-PGE2 A 0 20 LPS 15 pg/mL 10 5 0 B 3 Time 18 24 C Fig. 4. During induction of cyclooxygenase-2 expression, a cis-isomer of prostaglandin E2 is produced. A. The chemical structure of PGE2 having trans conformation of aliphatic chains at the cyclopentane ring. B. 8-iso-PGE2 with cis-conformation. C. Human bronchial epithelial cells were cultured at the presence of interleukin-1 or bacterial lipopolysaccharide, and 8-iso-PGE2 accumulated in the culture medium with a peak concentration between 3 and 18 hours, depending on the stimulus. occurs during induction of COX-2 enzyme, probably because the intracellular supply of arachidonic acid exceeds catalytic activity of cyclooxygenases. This is also due to inhibition of coexpressed COX-1 by NSAIDs. It requires a low basal level of COX-2, whose induction defect was recently described in fibroblasts of nasal polyps from AERD patients.45 This defect is attributed to a lowered density of the interleukin-1 receptor I and a failure to induce COX-2 and membrane-associated PGE synthase. All these abnormalities can be corrected in vitro by artificial expression of EP2, the PGE2 receptor type-2, which has been shown to be associated with AERD in genetic studies. The appropriate cellular model of these eicosanoid anomalies may help prove the mechanism of NSAIDs-triggered bronchoconstriction in AERD. Respiratory epithelial cells collected from asthmatic patients tend to maintain their epigenetic marks for several passages. Recently, these primary cell cultures have been obtained by nasal brushing instead of bronchofiberoscopy.47 However, the fundamental question regarding the mechanism of dysregulation of COX-2, mPGES, and EP2 as a plausible cause for AERD will require more studies. FUTURE DIRECTIONS IS THE RESEARCH ON EICOSANOID MEDIATORS IN ASTHMA The last decade progress in our understanding of the role of eicosanoids in asthma have stimulated development of methods for screening and measurements of these lipid mediators in complex biological matrices. It is rather improbable that any 
single eicosanoid or even a complex profile of eicosanoids could provide explanation for the mechanism of asthmatic inflammation. It remains rather a practical question whether profiling of eicosanoids in clinical samples will offer any advantages over other diagnostic methods. One of the currently tested biomarkers is urinary LTE4 that promises a diagnostic validity in distinguishing PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19808515 AERD patients from aspirin-tolerant asthmatics. The sensitivity and specificity of this biomarker seem to be limited. From the clinical and practical points of view, a limited positive predictive value of urinary LTE4 precludes any safe recommendation for the tolerance of NSAIDs to a PF-562271 web patient at risk for the disease. Another promising prediction based on urinary metabolites of eicosanoids is that systemic production of prostaglandins measured as a tetranor-PGE2 metabolite in urine, in children with wheezing, correlates with their risk for asthma. Systemic overproduction of PGE2 is associated with a suppressed ability of airway macrophages to phagocyte particulate matter carbon.46 A decreased number of the airway mac