The IL6R gene polymorphisms are associated with sIL-6R, IgE and lung function in Chinese patients with asthma

Wang, Yajun; Hu, Huiting; Wu, Jun; Zhao, Xuanna; Zhen, Yan; Wang, Shaobing; Li, Wen; Liang, Min; Wu, Bin; Ma, Guoda

doi:10.1016/j.gene.2016.03.026

Cited by 17 publications

(13 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…allergic sensitisation) and not during allergen‐induced exacerbations in atopic individuals. There is, however, some evidence against this possibility; rs2228145:C is associated with worse lung function in asthmatics, a finding that we found is supported by results from the UK Biobank study ( n = 31 471 Europeans with FEV 1 /FVC data; β = −0.026, SE = 0.007, P = 4.8 × 10 −4 ). Another level of complexity is that both mIL‐6R and sIL‐6R also bind the p28 subunit of IL‐27, with the sIL‐6R/p28 complex having antiviral activity .…”

Section: Discussionsupporting

confidence: 80%

“…69 Recently, we showed that rs2228145:C occurs at the same frequency in cases that suffer from asthma, hay fever or AD, therefore confirming its effect on the risk of multiple allergic diseases. 70 Lastly, there is also evidence that rs2228145:C is associated with more severe disease symptoms and decreased lung function in patients with asthma, 71,72 but not with the risk of chronic obstructive pulmonary disease. 64 In contrast to a predisposing effect on allergic disease, rs2228145:C is associated with decreased risk of coronary heart disease (OR = 0.95) 73 notably aortic aneurysms, atherosclerosis and myocardial infarction 74rheumatoid arthritis (RA; OR = 0.93) 75 and ankylosing spondylitis (OR = 0.88).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of interleukin‐6 receptor blockade on allergen‐induced airway responses in mild asthmatics

et al. 2019

View full text Add to dashboard Cite

Background Interleukin (IL)‐6 signalling has been implicated in allergic asthma by animal, genetic association and clinical studies. In this study, we tested the hypothesis that tocilizumab (TCZ), a human monoclonal antibody that blocks IL‐6 signalling, can prevent the development of allergen‐induced bronchoconstriction in humans. Methods We performed a randomised, double‐blind, placebo‐controlled study, with eligible participants completing two allergen inhalation challenge tests, conducted before and after treatment with a single dose of TCZ or placebo. The primary efficacy endpoint was the magnitude of the late asthmatic response recorded between 3 and 7 after allergen challenge. The secondary efficacy endpoint was the early asthmatic response, measured 20 min to 2 h after allergen challenge. Results A total of 66 patients enrolled between September 2014 and August 2017, when the trial was stopped for futility based on results from an interim analysis. Eleven patients fulfilled all eligibility criteria assessed at baseline and were subsequently randomised to the TCZ ( n = 6) or placebo ( n = 5) groups. Both the primary and secondary efficacy endpoints were not significantly different between the two groups. Five patients reported adverse events (AEs), three in the TCZ group (11 AEs) and two in the placebo group (four AEs). Only one AE was TCZ‐related (mild neutropenia), and there were no serious AEs. Significant treatment effects were observed for serum levels of C‐reactive protein, IL‐6 and soluble IL‐6R levels. Conclusion In a small proof‐of‐concept clinical trial, we found no evidence that a single dose of tocilizumab was able to prevent allergen‐induced bronchoconstriction. (Trial registered in the Australian New Zealand Clinical Trials Registry, number ACTRN12614000123640).

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Effects of interleukin‐6 receptor blockade on allergen‐induced airway responses in mild asthmatics

et al. 2019

View full text Add to dashboard Cite

show abstract

“…So far, as already cited above, STAT3, controlled by the EGFR/ADAM17 axis ( Figure 7 ), is a modifier of CF lung disease [ 221 ]. IL-6R, a prominent ADAM17 substrate linking the axis to STAT3 in trans-signaling, is a modifier of COPD as well as asthma [ 207 , 208 ]. So far, polymorphisms associated with the ADAM17, AREG, or EGFR genes have not been directly linked to chronic lung disease, but that may be due to limitations of the studies.…”

Section: Discussionmentioning

confidence: 99%

“…In COPD patients, elevated levels of IL-6R have been observed in peripheral blood leukocytes [ 205 ] and sputum samples [ 206 ]. Recently, genetic variants of IL-6R have been linked with lung function [ 207 ] and COPD severity [ 208 ]. In contrast to elevated IL-6R levels in sputum of COPD patients [ 207 ], the levels of sIL-6R in BALF from CF patients were not different in comparison to control, possibly due to enhanced degradation of sIL-6R by serine proteases [ 209 ].…”

Section: Role Of Il-6r In Human Lung Inflammation and Tissue Regenmentioning

confidence: 99%

“…Recently, genetic variants of IL-6R have been linked with lung function [ 207 ] and COPD severity [ 208 ]. In contrast to elevated IL-6R levels in sputum of COPD patients [ 207 ], the levels of sIL-6R in BALF from CF patients were not different in comparison to control, possibly due to enhanced degradation of sIL-6R by serine proteases [ 209 ]. Furthermore, it is not evident what the impact of luminal IL-6R on the activity of the subepithelial tissue is, which is separated from the lumen by tight junctions.…”

Section: Role Of Il-6r In Human Lung Inflammation and Tissue Regenmentioning

confidence: 99%

See 1 more Smart Citation

The EGFR-ADAM17 Axis in Chronic Obstructive Pulmonary Disease and Cystic Fibrosis Lung Pathology

Stolarczyk

Scholte

2018

Mediators of Inflammation

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) share molecular mechanisms that cause the pathological symptoms they have in common. Here, we review evidence suggesting that hyperactivity of the EGFR/ADAM17 axis plays a role in the development of chronic lung disease in both CF and COPD. The ubiquitous transmembrane protease A disintegrin and metalloprotease 17 (ADAM17) forms a functional unit with the EGF receptor (EGFR), in a feedback loop interaction labeled the ADAM17/EGFR axis. In airway epithelial cells, ADAM17 sheds multiple soluble signaling proteins by proteolysis, including EGFR ligands such as amphiregulin (AREG), and proinflammatory mediators such as the interleukin 6 coreceptor (IL-6R). This activity can be enhanced by injury, toxins, and receptor-mediated external triggers. In addition to intracellular kinases, the extracellular glutathione-dependent redox potential controls ADAM17 shedding. Thus, the epithelial ADAM17/EGFR axis serves as a receptor of incoming luminal stress signals, relaying these to neighboring and underlying cells, which plays an important role in the resolution of lung injury and inflammation. We review evidence that congenital CFTR deficiency in CF and reduced CFTR activity in chronic COPD may cause enhanced ADAM17/EGFR signaling through a defect in glutathione secretion. In future studies, these complex interactions and the options for pharmaceutical interventions will be further investigated.

show abstract

Hyper IgE Syndrome

Al‐Shaikhly

2021

Primary and Secondary Immunodeficiency

View full text Add to dashboard Cite

The IL6R gene polymorphisms are associated with sIL-6R, IgE and lung function in Chinese patients with asthma

Cited by 17 publications

References 59 publications

Effects of interleukin‐6 receptor blockade on allergen‐induced airway responses in mild asthmatics

Effects of interleukin‐6 receptor blockade on allergen‐induced airway responses in mild asthmatics

The EGFR-ADAM17 Axis in Chronic Obstructive Pulmonary Disease and Cystic Fibrosis Lung Pathology

Hyper IgE Syndrome

Contact Info

Product

Resources

About