Airway Goblet Cells Secrete Pro-Inflammatory Cytokines, Chemokines, and Growth Factors

Tanabe, Tsuyoshi; Rubin, Bruce K.

doi:10.1378/chest.15-0947

Cited by 39 publications

(25 citation statements)

References 27 publications

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“…Furthermore, airway goblet cells are proinflammatory effector cells which are able to secrete pro-inflammatory cytokines, chemokines, and growth factors. These inflammatory mediators released from goblet cells may act in an autocrine and paracrine manner to enhance inflammation in diseases such as asthma and leading to airway goblet cell hyperplasia (20,21). Our findings therefore present pathological evidences to the current "vicious cycle hypothesis" in the development of bronchiectasis.…”

Section: Discussionsupporting

confidence: 58%

Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

Chen

Wang

et al. 2018

J. Thorac. Dis.

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Background: Aberrant epithelial remodeling and/or abnormalities in mucociliary apparatus in airway epithelium contribute to infection and inflammation. It is uncertain if these changes occur in both large and small airways in non-cystic fibrosis bronchiectasis (non-CF bronchiectasis). In this study, we aim to investigate the histopathology and inflammatory profile in the epithelium of bronchi and bronchioles in bronchiectasis.Methods: Excised lung tissue sections from 52 patients with non-CF bronchiectasis were stained with specific cellular markers and analyzed by immunohistochemistry and immunofluorescence to assess the epithelial structures, including ciliated cells and goblet cells morphology. Inflammatory cell counts and ciliary proteins expression levels of centrosomal protein 110 (CP110) and dynein heavy chain 5, axonemal (DNAH5) were assessed.Results: Epithelial hyperplasia is found in both bronchi and bronchioles in all specimens, including hyperplasia and/or hypertrophy of goblet cells. The median cilia length is longer in hyperplastic epithelium [bronchi: 8.16 (7.03-9.14) μm, P<0.0001; bronchioles: 7.46 (6.41-8.48) μm, P<0.0001] as compared to nonhyperplastic epithelium (bronchi: 5.60 μm; bronchioles: 4.89 μm). Hyperplastic epithelium is associated with overexpression of CP110 and decreased intensity of DNAH5 expression in both bronchial and bronchiolar epithelium. Though infiltration of neutrophils is predominant (63.0% in bronchi and 76.7% in bronchioles), eosinophilic infiltration is also present in the mucosa of bronchi (30.8%) and bronchioles (54.8%).Conclusions: Aberrant epithelial remodeling with impaired mucociliary architecture is present in both large and small airways in patients with refractory non-CF bronchiectasis. Future studies should evaluate the interplay between these individual components in driving chronic inflammation and lung damage in patients.

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Section: Discussionsupporting

confidence: 58%

Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

Chen

Wang

et al. 2018

J. Thorac. Dis.

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“…In agreement with other reports, Ccl2 expression was observed in colonic epithelial cells, especially in goblet cells [ 2 , 5 ]. Goblet cells produce not only mucin, but also pro-inflammatory cytokines and chemokines during stress conditions [ 26 ]. Recent reports show that alteration of histone modification, such as acetylation and methylation, in colonic epithelial cells is important for onset and progression of colitis [ 24 , 25 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

The HDAC Inhibitor, SAHA, Prevents Colonic Inflammation by Suppressing Pro-inflammatory Cytokines and Chemokines in DSS-induced Colitis

Ali

Choijookhuu

Takagi

et al. 2018

Acta Histochemica et Cytochemica

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Inflammatory bowel disease (IBD) is an inflammatory disorder of the gastrointestinal tract that is caused by multiple factors, including dysfunction of the immune system and genetic and epigenetic alterations. Aberrant epigenetic regulation, especially histone acetylation, was found in biopsies from IBD patients and mouse models of colitis, suggesting that an epigenetic treatment approach may be useful for IBD therapy. Therefore, we investigated the effects of the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), in a mouse model of dextran sulfate sodium (DSS)-induced colitis. C57BL/6 mice were treated with 1.5% DSS for 5 days and/or SAHA (25 mg/kg BW/day) for 26 days. Levels of mRNA for the pro-inflammatory cytokines, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and the chemokines, Ccl2, were examined by qRT-PCR. CD11b, a marker of dendritic cells, macrophages, and monocytes, as well as Ccl2 expression, were examined by immunohistochemistry. IL-6, TNF-α, and Ccl2 gene expression peaked on day 5 in DSS-treated mouse colon, whereas SAHA treatment significantly decreased pro-inflammatory gene expression. Ccl2 protein expression resembled Ccl2 gene expression results. Moreover, localization of CD11b showed that migratory inflammatory cells were dramatically decreased by SAHA treatment compared to DSS-treated mouse colon. Thus, we conclude that the HDAC inhibitor, SAHA, attenuates inflammatory changes in DSS-induced colitis by suppressing local secretion of pro-inflammatory cytokines and chemokines and also by suppressing mobilization and accumulation of inflammatory cells.

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“…Moreover, APCs are in close contact with the upper airway epithelium, 107 and increased differentiation of GCs lead to the recruitment of APCs to the airway epithelium, 108 suggesting that the presence of GCs might recruit APCs facilitating interactions and antigen transfer. In addition, airway GCs secrete multiple cytokines and chemokines, recruiting immune cells and shaping the immune response to inhaled antigens, [108][109][110] suggesting that like intestinal GCs upper airway GCs may deliver antigens to APCs and direct the phenotype of the immune response. Like the intestine and conjunctiva, the lung has its own unique, though limited, microbiota, 111 which can become dysbiotic and expanded in disease or harbor pathogens and represent potential danger, 112,113 raising the possibility that airway GCs may also respond to microbial signals to modulate immune responses to inhaled antigens.…”

Section: Can Gcs At Other Mucosal Surfaces Form Gaps?mentioning

confidence: 99%

Goblet cells: multifaceted players in immunity at mucosal surfaces

2018

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Goblet cells (GCs) are specialized epithelial cells that line multiple mucosal surfaces and have a well-appreciated role in barrier maintenance through the secretion of mucus. Moreover, GCs secrete anti-microbial proteins, chemokines, and cytokines demonstrating functions in innate immunity beyond barrier maintenance. Recently it was appreciated that GCs can form goblet cell-associated antigen passages (GAPs) and deliver luminal substances to underlying lamina propria (LP) antigen-presenting cells (APCs) in a manner capable of inducing adaptive immune responses. GCs at other mucosal surfaces share characteristics with the GAP forming intestinal GCs, suggesting that GAP formation may not be restricted to the gut, and that GCs may perform this gatekeeper function at other mucosal surfaces. Here we review observations of how GCs contribute to immunity at mucosal surfaces through barrier maintenance, the delivery of luminal substances to APCs, interactions with APCs, and secretion of factors modulating immune responses.

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Airway Goblet Cells Secrete Pro-Inflammatory Cytokines, Chemokines, and Growth Factors

Cited by 39 publications

References 27 publications

Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

The HDAC Inhibitor, SAHA, Prevents Colonic Inflammation by Suppressing Pro-inflammatory Cytokines and Chemokines in DSS-induced Colitis

Goblet cells: multifaceted players in immunity at mucosal surfaces

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