IL‐13 induced increases in nitrite levels are primarily driven by increases in inducible nitric oxide synthase as compared with effects on arginases in human primary bronchial epithelial cells

Chibana, Kazuyuki; Trudeau, John B.; Mustovitch, A. T.; Hu, Hongsheng; Zhao, Jiang; Balzar, Silvana; Chu, Hang; Wenzel, Sally E.

doi:10.1111/j.1365-2222.2008.03071.x

Cited by 36 publications

(42 citation statements)

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“…There were previously reported that OVA increased the breathing resistance of the mice [11], resistive breathing induced IL-4 expression in diaphragm muscle [12], Th2 cytokines such as IL-4 and IL-13 induce iNOS expression through the STAT-6 pathway [13][14][15][16][17], iNOS reduced diaphragm muscle contraction, inhibition of iNOS induction and inhibition of NOS activity prevented diaphragm muscle contractile dysfunction [18]. Study results of ours are in agreement with study that previously reported.…”

Section: Discussionsupporting

confidence: 83%

Diaphragm Muscle Contraction Decrease in a Mouse Model of Ovalbumin-Induced Allergic Airway Inflammation

Yamaguchi¹,

Shindoh²,

Miura³

2017

J Allergy Ther

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Objective: We investigated diaphragm contractile and inflammatory properties of mice with OVA sensitization and challenge.Methods: BALB/c mice were sensitized to OVA by intraperitoneal (i.p.) injection at 0 and 7 days, and challenged with aerosolized OVA on 21, 22, and 23 days (O/O group). Budesonide/Formoterol combination was inhaled on days 21, 22, and 23 before OVA challenge on those same days (O/OC group). Control mice were sensitized and challenged with an aerosolized saline (O-group). The diaphragm contractile and inflammatory properties were measured on day 24. NOS activity in the diaphragm muscle was evaluated by NADPH diaphorase staining. IL-4 and IL-13 levels of BALF, as well as lung tissue and diaphragm muscle homogenates were measured by ELISA. Conclusions:OVA sensitization and challenge decreased diaphragm muscle contraction, increased NOS activity, IL-4 levels of diaphragm in a mouse model. Budesonide/Formoterol combination could protect diaphragm muscle weakness and inflammation. According to the traditional concept of the contemporary Immunology, neither autoimmune diseases nor allergic diseases can be cured completely. Nevertheless, a fortunate coincidence led me to discovery of a novel concept that eliminations of the causes of these diseases are possible. In other words, combinations of pathogenic antibodies with responsible cells, namely, cytolytic T lymphocytes in cases of autoimmune diseases and mast cells in cases of allergic diseases, can be decomposed by replacing the pathogenic antibodies with non-specific antibodies. In more detail, intradermal injections with a non-specific antigen preparation induce production of non-specific antibodies in the body of the patient. Repetitions of the injections bring about an accumulation of them. Accumulated non-specific antibodies will occupy most of the receptors on the surface of responsible cells. When the accumulation reaches the sufficient level, virtually no pathogenic antibodies would remain on the receptors. That is, no causes of the diseases remain. Naturally, where there is no cause, there is no disease. Details are demonstrated elsewhere.

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Section: Discussionsupporting

confidence: 83%

Diaphragm Muscle Contraction Decrease in a Mouse Model of Ovalbumin-Induced Allergic Airway Inflammation

Yamaguchi¹,

Shindoh²,

Miura³

2017

J Allergy Ther

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“…Endobronchial tissue for immunohistochemistry (IHC) was collected at all the SARP sites listed above, whereas tissue and epithelial cell samples for mRNA were collected only at the National Jewish Health and then the University of Pittsburgh site. Epithelial cells were obtained by brushing the proximal airways as previously described (28). The cells were placed in Trizol (Invitrogen, Carlsbad, CA) for extraction of mRNA.…”

Section: Bronchoscopy Bal and Sample Processingmentioning

confidence: 99%

“…These procedures were performed across sites according to previously published protocols and the SARP manual of procedures (4,6,27,28). Endobronchial tissue for immunohistochemistry (IHC) was collected at all the SARP sites listed above, whereas tissue and epithelial cell samples for mRNA were collected only at the National Jewish Health and then the University of Pittsburgh site.…”

Section: Bronchoscopy Bal and Sample Processingmentioning

confidence: 99%

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Mast Cell Phenotype, Location, and Activation in Severe Asthma

Balzar¹,

Fajt²,

Comhair³

et al. 2011

Am J Respir Crit Care Med

269

242

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Rationale: Severe asthma (SA) remains poorly understood. Mast cells (MC) are implicated in asthma pathogenesis, but it remains unknown how their phenotype, location, and activation relate to asthma severity. Objectives: To compare MC-related markers measured in bronchoscopically obtained samples with clinically relevant parameters between normal subjects and subjects with asthma to clarify their pathobiologic importance. Methods: Endobronchial biopsies, epithelial brushings, and bronchoalveolar lavage were obtained from subjects with asthma and normal subjects from the Severe Asthma Research Program (N 5 199). Tryptase, chymase, and carboxypeptidase A (CPA)3 were used to identify total MC (MC Tot ) and the MC TC subset (MCs positive for both tryptase and chymase) using immunostaining and quantitative real-time polymerase chain reaction. Lavage was analyzed for tryptase and prostaglandin D2 (PGD2) by ELISA. Measurements and Main Results: Submucosal MC Tot (tryptase-positive by immunostaining) numbers were highest in ''mild asthma/no inhaled corticosteroid (ICS) therapy'' subjects and decreased with greater asthma severity (P 5 0.002). In contrast, MC TC (chymasepositive by immunostaining) were the predominant (MC TC /MC Tot . 50%) MC phenotype in SA (overall P 5 0.005). Epithelial MC Tot were also highest in mild asthma/no ICS, but were not lower in SA. Instead, they persisted and were predominantly MC TC . Epithelial CPA3 and tryptase mRNA supported the immunostaining data (overall P 5 0.008 and P 5 0.02, respectively). Lavage PGD2 was higher in SA than in other steroid-treated groups (overall P 5 0.02), whereas tryptase did not differentiate the groups. In statistical models, PGD2 and MC TC /MC Tot predicted SA. Conclusions: Severe asthma is associated with a predominance of MC TC in the airway submucosa and epithelium. Activation of those MC TC may contribute to the increases in PGD2 levels. The data suggest an altered and active MC population contributes to SA pathology.

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“…Its inhibition in vivo by biologic therapies targeted toward IL-4 and -13 confirms its association with this immune pathway (14)(15)(16)(17). However, FE NO elevation is observed across a range of disease states, including a high-risk asthma phenotype, CS refractory asthma, and even atopy without asthma (18,19).…”

mentioning

confidence: 99%

Gene Expression in Relation to Exhaled Nitric Oxide Identifies Novel Asthma Phenotypes with Unique Biomolecular Pathways

Modena

Tedrow

Milošević

et al. 2014

Am J Respir Crit Care Med

169

178

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Rationale: Although asthma is recognized as a heterogeneous disease associated with clinical phenotypes, the molecular basis of these phenotypes remains poorly understood. Although genomic studies have successfully broadened our understanding in diseases such as cancer, they have not been widely used in asthma studies.Objectives: To link gene expression patterns to clinical asthma phenotypes.Methods: We used a microarray platform to analyze bronchial airway epithelial cell gene expression in relation to the asthma biomarker fractional exhaled nitric oxide (FE NO ) in 155 subjects with asthma and healthy control subjects from the Severe Asthma Research Program (SARP). Measurements and Main Results:We first identified a diverse set of 549 genes whose expression correlated with FE NO . We used k-means to cluster the patient samples according to the expression of these genes, identifying five asthma clusters/phenotypes with distinct clinical, physiological, cellular, and gene transcription characteristics-termed "subject clusters" (SCs). To then investigate differences in gene expression between SCs, a total of 1,384 genes were identified that highly differentiated the SCs at an unadjusted P value , 1026 . Hierarchical clustering of these 1,384 genes identified nine gene clusters or "biclusters," whose coexpression suggested biological characteristics unique to each SC. Although genes related to type 2 inflammation were present, novel pathways, including those related to neuronal function, WNT pathways, and actin cytoskeleton, were noted.Conclusions: These findings show that bronchial epithelial cell gene expression, as related to the asthma biomarker FE NO , can identify distinct asthma phenotypes, while also suggesting the presence of underlying novel gene pathways relevant to these phenotypes.

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IL‐13 induced increases in nitrite levels are primarily driven by increases in inducible nitric oxide synthase as compared with effects on arginases in human primary bronchial epithelial cells

Abstract: . IL-13 induced increases in nitrite levels are primarily driven by increases in inducible nitric oxide synthase as compared with effects in arginases in human primary bronchial epithelial cells. Clin Exp Allergy 2008; 936-46.

Cited by 36 publications

References 0 publications

Diaphragm Muscle Contraction Decrease in a Mouse Model of Ovalbumin-Induced Allergic Airway Inflammation

Diaphragm Muscle Contraction Decrease in a Mouse Model of Ovalbumin-Induced Allergic Airway Inflammation

Mast Cell Phenotype, Location, and Activation in Severe Asthma

Gene Expression in Relation to Exhaled Nitric Oxide Identifies Novel Asthma Phenotypes with Unique Biomolecular Pathways

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