Role of periostin, FENO, IL-13, lebrikzumab, other IL-13 antagonist and dual IL-4/IL-13 antagonist in asthma

Agrawal, Swati; Townley, Robert G.

doi:10.1517/14712598.2014.859673

Cited by 41 publications

(28 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the mechanisms of periostin in AERD are not fully understood, it is proposed that exposure to Th2-driven inflammation enhances the overexpression of the POSTN gene, resulting an increased level of periostin21. In addition, IL-13 may induce release of periostin from bronchial epithelial cells32. S1P is known to be associated with airway hyperactivity and Th2 cytokines in mouse lung101133.…”

Section: Discussionmentioning

confidence: 99%

Exploration of the Sphingolipid Metabolite, Sphingosine-1-phosphate and Sphingosine, as Novel Biomarkers for Aspirin-exacerbated Respiratory Disease

Trinh

Kim

Cho

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Sphingolipid (SL) metabolites have been suggested to be important inflammatory mediators in airway inflammation and asthma. However, little is known about SL metabolites in aspirin-exacerbated respiratory disease (AERD). We aimed to explore the potential AERD biomarkers by conducting lipidomics targeting SL metabolites. The levels of SL metabolites in serum and urine samples from 45 AERD patients and 45 aspirin-tolerant asthma (ATA) patients were quantified through mass spectrometry. During the lysine-aspirin bronchoprovocation test (ASA-BPT), the levels of serum sphingomyelin (SM) were significantly decreased in AERD (P < 0.05) but not in ATA. The serum SM levels were positively correlated with airway responsiveness to methacholine. At the basal status before the ASA-BPT, the levels of serum sphingosine-1-phosphate (S1P) and urine sphingosine were significantly higher in the AERD patients compared with that of ATA patients (P < 0.001) and were positively correlated with a greater decrease in FEV1 (%) values following the ASA-BPT test (P < 0.001 for each), and with serum periostin level (P < 0.05 for each). This study is the first to evaluate serum S1P and urine sphingosine as potential biomarkers of AERD as well as to examine the metabolic disturbance of SL in AERD patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Exploration of the Sphingolipid Metabolite, Sphingosine-1-phosphate and Sphingosine, as Novel Biomarkers for Aspirin-exacerbated Respiratory Disease

Trinh

Kim

Cho

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Its expression is elevated in human bronchial epithelial cells in association with increased expression of IL-5 and IL-13 in the submucosa (44,45). Serum periostin is a better predictor of airway eosinophilia in SA than FeNO is, although blood eosinophils are also reasonably predictive (46,47). Therefore, it is not yet clear which biomarker will best identify Type-2 immune-inflammation in SA.…”

Section: Inflammatory Processes: Pathobiological Evidence For Type-2 mentioning

confidence: 99%

Pathobiology of Severe Asthma

Bittar¹,

Yousem²,

Wenzel

2015

Annu. Rev. Pathol. Mech. Dis.

107

View full text Add to dashboard Cite

Severe asthma (SA) afflicts a heterogeneous group of asthma patients who exhibit poor responses to traditional asthma medications. SA patients likely represent 5-10% of all asthma patients; however, they have a higher economic burden when compared with milder asthmatics. Considerable research has been performed on pathological pathways and structural changes associated with SA. Although limitations of the pathological approaches, ranging from sampling, to quantitative assessments, to heterogeneity of disease, have prevented a more definitive understanding of the underlying pathobiology, studies linking pathology to molecular markers to targeted therapies are beginning to solidify the identification of select molecular phenotypes. This review addresses the pathobiology of SA and discusses the current limitations of studies, the inflammatory cells and pathways linked to emerging phenotypes, and the structural and remodeling changes associated with severe disease. In all cases, an effort is made to link pathological findings to specific clinical/molecular phenotypes.

show abstract

“…Recent studies have suggested that periostin modulates Th2-mediated asthma pathogenesis by assisting in the recruitment of inflammatory cells, particularly eosinophils, to the lungs [34]. Moreover, periostin is known to facilitate the activation of dendritic cells, thereby rendering airway hyperresponsiveness and airway inflammation in mice [35, 36]. Beside, we discovered an increased serum level of MPO in the ABCC4 −1508G allele carriers comparing to that of noncarriers.…”

Section: Discussionmentioning

confidence: 67%

A Role of the ABCC4 Gene Polymorphism in Airway Inflammation of Asthmatics

Palikhe

Udval

Trinh

et al. 2017

Mediators of Inflammation

View full text Add to dashboard Cite

The ATP-binding cassette subfamily C member 4 gene encodes a transmembrane protein involved in the export of proinflammatory molecules, including leukotriene, prostaglandin, and sphingosine-1-phosphate across the plasma membrane. Those metabolites play important roles in asthma. We investigated the potential associations between ABCC4 gene polymorphisms and asthma phenotype. In total, 270 asthma patients and 120 normal healthy controls were enrolled for a genetic association study. Two polymorphisms (−1508A>G and −642C>G) in the ABCC4 promoter were genotyped. The functional variability of the promoter polymorphisms was analyzed by luciferase reporter assay. Inflammatory cytokine levels were measured by enzyme-linked immunosorbent assay. Serum and urinary eicosanoid metabolites, sphingosine-1-phosphate, were evaluated by quadrupole time-of-flight mass spectrometry. Asthma patients carrying the G allele at −1508A>G had significantly higher serum levels of periostin, myeloperoxidase, and urinary levels of 15-hydroxyeicosatetraenoic acid and sphingosine-1-phosphate (P = 0.016, P = 0.027, P = 0.032, and P = 0.010, resp.) compared with noncarrier asthma patients. Luciferase activity was significantly enhanced in human epithelial A549 cells harboring a construct containing the −1508G allele (P < 0.01 for each) compared with a construct containing the −1508A allele. A functional polymorphism in the ABCC4 promoter, −1508A>G, may increase extracellular 15-hydroxyeicosatetraenoic acid, sphingosine-1-phosphate, and periostin levels, contributing to airway inflammation in asthmatics.

show abstract

Role of periostin, FENO, IL-13, lebrikzumab, other IL-13 antagonist and dual IL-4/IL-13 antagonist in asthma

Abstract: Lebrikizumab block IL-13 signaling through the IL-13Rα1/IL-4Rα receptor. There was a larger reduction in FENO in the high periostin subgroup than in the low periostin subgroup (34.4 vs 4.3%). Serum CCL17, CCL13 and total IgE levels decreased in the lebrikizumab group.

Cited by 41 publications

References 69 publications

Exploration of the Sphingolipid Metabolite, Sphingosine-1-phosphate and Sphingosine, as Novel Biomarkers for Aspirin-exacerbated Respiratory Disease

Exploration of the Sphingolipid Metabolite, Sphingosine-1-phosphate and Sphingosine, as Novel Biomarkers for Aspirin-exacerbated Respiratory Disease

Pathobiology of Severe Asthma

A Role of the ABCC4 Gene Polymorphism in Airway Inflammation of Asthmatics

Contact Info

Product

Resources

About