Enhanced 15-Lipoxygenase 1 Production is Related to Periostin Expression and Eosinophil Recruitment in Eosinophilic Chronic Rhinosinusitis

Imoto, Yoshimasa; Takabayashi, Tetsuji; Sakashita, Masafumi; Kato, Yoshio; Yoshida, Kanako; Kidoguchi, Masanori; Koyama, Keisuke; Adachi, Naoto; Kimura, Yukihiro; Ogi, Kazuhiro; Ito, Yatsuji; Kanno, Masafumi; Okamoto, Masayuki; Narita, Norihiko; Fujieda, Shigeharu

doi:10.3390/biom10111568

Cited by 19 publications

(18 citation statements)

References 55 publications

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“…Evidence from previous data shows that IL-13 stimulation induces 15-LO expression in epithelial cells resulting in CCL26 production ( 53 ). It is, thus, conceivable that the interplay of upregulated IL13 levels in MC drives the 15-LO-mediated expression of CCL26 and POSTN in epithelial cells resulting in eosinophil recruitment ( 53 , 54 ). MC cluster MC2 in AERD also showed signs of a recently described inflammatory CD117 high CD38 high subepithelial MC T phenotype, which is specifically expanded during T2 inflammation ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Nasal Polyps Reveals a More Pronounced Type 2 Transcriptomic Profile of Epithelial Cells and Mast Cells in Aspirin-Exacerbated Respiratory Disease

et al. 2022

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Chronic rhinosinusitis with nasal polyps is affecting up to 3% of Western populations. About 10% of patients with nasal polyps also suffer from asthma and intolerance to aspirin, a syndrome called aspirin-exacerbated respiratory disease. Although eosinophilic inflammation is predominant in polyps of both diseases, phenotypic differences in the tissue-derived microenvironment, elucidating disease-specific characteristics, have not yet been identified. We sought to obtain detailed information about phenotypic and transcriptional differences in epithelial and immune cells in polyps of aspirin-tolerant and intolerant patients. Cytokine profiles in nasal secretions and serum of patients suffering from aspirin-exacerbated respiratory disease (n = 10) or chronic rhinosinusitis with nasal polyps (n = 9) were assessed using a multiplex mesoscale discovery assay. After enrichment for immune cell subsets by flow cytometry, we performed transcriptomic profiling by employing single-cell RNA sequencing. Aspirin-intolerant patients displayed significantly elevated IL-5 and CCL17 levels in nasal secretions corresponding to a more pronounced eosinophilic type 2 inflammation. Transcriptomic profiling revealed that epithelial and mast cells not only complement one another in terms of gene expression associated with the 15-lipoxygenase pathway but also show a clear type 2-associated inflammatory phenotype as identified by the upregulation of POSTN, CCL26, and IL13 in patients with aspirin-exacerbated respiratory disease. Interestingly, we also observed cellular stress responses indicated by an increase of MTRNR2L12, MTRNR2L8, and NEAT1 across all immune cell subsets in this disease entity. In conclusion, our findings support the hypothesis that epithelial and mast cells act in concert as potential drivers of the pathogenesis of the aspirin-exacerbated respiratory disease.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Nasal Polyps Reveals a More Pronounced Type 2 Transcriptomic Profile of Epithelial Cells and Mast Cells in Aspirin-Exacerbated Respiratory Disease

et al. 2022

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“…However, the mRNA expression of the ST2 , IL-33 receptor significantly increased in NP tissue of eosinophilic CRSwNP patients [ 51 ]. IL-33 is believed to enhance levels of 15-lipoxygenase 1 in acute myeloid (eosinophilic) leukemia cells, a compound known to facilitate inflammatory processes in eosinophilic CRSwNP patients [ 52 ]. Conversely, inhibition of IL-33 in a mouse model was found to reduce Th2 cell count [ 53 ], subepithelial collagen deposition and oedematous mucosa thickness [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Serum IL-5, POSTN and IL-33 levels in chronic rhinosinusitis with nasal polyposis correlate with clinical severity

Zielińska‐Bliźniewska

Paprocka-Zjawiona

Merecz-Sadowska

et al. 2022

BMC Immunol

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Background Chronic rhinosinusitis (CRS) is a group of heterogeneous diseases characterized by epithelial inflammation and tissue eosinophilic infiltration. IL-5, POSTN, and IL-33 are important factors that act as chemoattractants for eosinophils, and a tissue-remodeling protein positively correlated with eosinophils in blood and mediators of eosinophilic infiltration. The aim of the study was to determine the expression of IL-5, POSTN and IL-33, at the gene and protein levels, in eosinophilic CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP), and to correlate this expression with clinical severity. Materials and methods The study included 40 CRSwNP patients and 53 CRSsNP patients and 40 control subjects. The expression of IL-5, POSTN and IL-33 mRNA was determined in sinonasal mucosal samples and in nasal polyp tissue by real-time PCR. Protein levels in the serum of CRSwNP patients were measured by ELISA. Computed tomography was evaluated according to Lund–Mackay scores, and visual analog scale scores were assessed. Results NP tissue demonstrated significantly higher IL-5 and POSTN mRNA expression than the sinonasal tissue in the CRSsNP and CRSwNP groups. CRS groups demonstrated elevated IL-33 mRNA expression in comparison to controls irrespective of the presence of NP. No correlation was found between IL-5, POSTN and IL-33 mRNA expression and disease severity. CRSwNP group demonstrated significantly higher serum IL-5, POSTN and IL-33 protein levels than controls, and this corresponds to disease severity. Conclusion Serum IL-5, POSTN and IL-33 levels may be important markers for classification of eosinophilic CRSwNP patients, along with disease severity.

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“…Patients with higher ALOX-15 expression suffered from a worse CRSwNP disease with higher number of sinus operations and worse inflammation in the sinus CT scans ( 19 ). The expression level of ALOX-15 mRNA was significantly higher in eosinophilic polyps and could distinguish between eosinophilic and non-eosinophilic nasal polyps ( 27 ). The expression of 15-LO was seen in both the epithelial cells and eosinophils in nasal polyp tissue detected by immunohistochemical staining ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

“…The expression level of ALOX-15 mRNA was significantly higher in eosinophilic polyps and could distinguish between eosinophilic and non-eosinophilic nasal polyps ( 27 ). The expression of 15-LO was seen in both the epithelial cells and eosinophils in nasal polyp tissue detected by immunohistochemical staining ( 27 ). Dupilumab, a biological drug for treating asthma, atopic dermatitis and CRSwNP, suppresses IL-4 and IL-13 signaling, on which the expression of ALOX-15 is strictly dependent ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

Pathomechanisms of AERD—Recent Advances

2021

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The pathomechanisms behind NSAID-exacerbated respiratory disease are complex and still largely unknown. They are presumed to involve genetic predisposition and environmental triggers that lead to dysregulation of fatty acid and lipid metabolism, altered cellular interactions involving transmetabolism, and continuous and chronic inflammation in the respiratory track. Here, we go through the recent advances on the topic and sum up the current understanding of the background of this illness that broadly effects the patients' lives.

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Enhanced 15-Lipoxygenase 1 Production is Related to Periostin Expression and Eosinophil Recruitment in Eosinophilic Chronic Rhinosinusitis

Cited by 19 publications

References 55 publications

Comprehensive Analysis of Nasal Polyps Reveals a More Pronounced Type 2 Transcriptomic Profile of Epithelial Cells and Mast Cells in Aspirin-Exacerbated Respiratory Disease

Comprehensive Analysis of Nasal Polyps Reveals a More Pronounced Type 2 Transcriptomic Profile of Epithelial Cells and Mast Cells in Aspirin-Exacerbated Respiratory Disease

Serum IL-5, POSTN and IL-33 levels in chronic rhinosinusitis with nasal polyposis correlate with clinical severity

Pathomechanisms of AERD—Recent Advances

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