Association of autophagy related gene polymorphisms with neutrophilic airway inflammation in adult asthma

Pham, Duy Le; Kim, Seung Hyun; Losol, Purevsuren; Yang, Eun Mi; Shin, Yoo Seob; Ye, Young-Min; Park, Hae‐Sim

doi:10.3904/kjim.2014.390

Cited by 53 publications

(54 citation statements)

References 36 publications

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“…Furthermore, the finding that Dex and CAM induced autophagy in neutrophils was consistent with the previous reports . We suggested previously that autophagy‐related ( ATG ) 5 and ATG7 polymorphisms could contribute to neutrophil activation and function . Consistently, deleting Atg5 and Atg7 in mice was found to reduce neutrophil degranulation and neutrophil‐mediated inflammation .…”

Section: Discussionsupporting

confidence: 91%

“…Atopy was identified as described previously . Sputum neutrophil and eosinophil counts were evaluated as described in a previous study .…”

Section: Methodsmentioning

confidence: 99%

“…Subjects with comorbidities or those having used systemic corticosteroids and other immunosuppressants or biologics were excluded from the study. Atopy was identified as described previously [12]. Sputum neutrophil and eosinophil counts were evaluated as described in a previous study [12].…”

Section: Study Subjectsmentioning

confidence: 99%

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Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma

Pham

Ban

Kim

et al. 2016

Clin Experimental Allergy

154

126

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SummaryBackground Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated. Objectives We compared autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non-severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs). Methods Peripheral blood neutrophils from patients with SA (n = 30) and NSA (n = 38) were treated with interleukin (IL)-8 (100 ng/mL). Autophagy (light chain 3-II expression) and NET production levels were evaluated by Western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin-1, and IL-8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). Results Untreated and IL-8-treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P < 0.01). IL-8 increased autophagy and NET levels in PBNs from the SA group, but not from the NSA group. NET levels were correlated with autophagy levels in PBNs (P < 0.001). IL-8-induced NET production levels negatively were correlated with FEV1/FVC (r = À0.700, P = 0.016). NETs induced cell death, detachment, degradation of occludin and claudin-1, and IL-8 production from AECs. Higher levels of NET-induced ECP and EDN were released from PBEs in SA compared with NSA groups. Conclusions and Clinical Relevance Neutrophil autophagy and NETs could enhance asthma severity by damaging airway epithelium and triggering inflammatory responses of AECs and PBEs. Modulating neutrophil autophagy and NET production may be a new target therapy for SA.

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Section: Discussionsupporting

confidence: 91%

“…Atopy was identified as described previously . Sputum neutrophil and eosinophil counts were evaluated as described in a previous study .…”

Section: Methodsmentioning

confidence: 99%

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Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma

Pham

Ban

Kim

et al. 2016

Clin Experimental Allergy

154

126

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“…How autophagy shapes the inflammatory response has been discussed in various disease models6789, and several studies have focused on the functional link between autophagy and inflammation-associated pulmonary pathogenesis, which suggest a critical role of autophagy in inflammation regulation in pulmonary diseases like asthma and acute lung injury (ALI)1011. On the other hand, emerging investigations have demonstrated that autophagy can be activated by CS in lung cells1213, acting as a deleterious process during COPD pathogenesis such as the apoptosis of lung epithelial cells1314.…”

mentioning

confidence: 99%

Silymarin attenuates cigarette smoke extract-induced inflammation via simultaneous inhibition of autophagy and ERK/p38 MAPK pathway in human bronchial epithelial cells

Wang

et al. 2016

Sci Rep

101

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Cigarette smoke (CS) is a major risk of chronic obstructive pulmonary disease (COPD), contributing to airway inflammation. Our previous study revealed that silymarin had an anti-inflammatory effect in CS-exposed mice. In this study, we attempt to further elucidate the molecular mechanisms of silymarin in CS extract (CSE)-induced inflammation using human bronchial epithelial cells. Silymarin significantly suppressed autophagy activation and the activity of ERK/p38 mitogen-activated protein kinase (MAPK) pathway in Beas-2B cells. We also observed that inhibiting the activity of ERK with specific inhibitor U0126 led to reduced autophagic level, while knockdown of autophagic gene Beclin-1 and Atg5 decreased the levels of ERK and p38 phosphorylation. Moreover, silymarin attenuated CSE-induced upregulation of inflammatory cytokines TNF-α, IL-6 and IL-8 which could also be dampened by ERK/p38 MAPK inhibitors and siRNAs for Beclin-1 and Atg5. Finally, we validated decreased levels of both autophagy and inflammatory cytokines (TNF-α and KC) in CS-exposed mice after silymarin treatment. The present research has demonstrated that CSE-induced autophagy in bronchial epithelia, in synergism with ERK MAPK pathway, may initiate and exaggerate airway inflammation. Silymarin could attenuate inflammatory responses through intervening in the crosstalk between autophagy and ERK MAPK pathway, and might be an ideal agent treating inflammatory pulmonary diseases.

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“…Abundant studies reported that airway neutrophilic inflammation was associated with asthma phenotypes/endotypes, severe asthma, asthma exacerbations, and corticosteroid treatment responses [38] .…”

Section: Involvement Of Neutrophils In Airway Inflammation Of Asthmamentioning

confidence: 99%

Aberrant function of neutrophils in asthma

wang

Zhao

Xie

2018

Inflamm Cell Signal

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Asthma is a chronic inflammatory airway disease, with an array of cells involved in the pathogenesis. The role of neutrophils in asthma pathogenesis is controversial. This review highlights the mechanisms of neutrophils about their aberrant function in asthma and factors contributing to impaired response to corticosteroids, which may contribute to a better understanding of asthma pathogenesis and consequently, facilitate the development of novel strategies for managing and treating neutrophilia in asthma.

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Association of autophagy related gene polymorphisms with neutrophilic airway inflammation in adult asthma

Cited by 53 publications

References 36 publications

Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma

Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma

Silymarin attenuates cigarette smoke extract-induced inflammation via simultaneous inhibition of autophagy and ERK/p38 MAPK pathway in human bronchial epithelial cells

Aberrant function of neutrophils in asthma

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