Association of interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in Turkish children with atopic asthma

Zeyrek, Dost; Demir, Esen; Alpman, Asude; Özkınay, Ferda; Gülen, Figen; Tanaç, Remziye

doi:10.2500/aap.2008.29.3154

Cited by 22 publications

(15 citation statements)

References 22 publications

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“…In asthmatic subjects, the NO-producing MDRC populations B & C produced ~400-fold more IL-6 than their counterparts purified from COPD or normal samples or compared to ROS-producing MDRC. IL-1β, a proinflammatory signature cytokine for MDRC that has been implicated in the pathogenesis of asthma, 35 was increased in BAL MDRC culture supernatants from asthmatics compared to COPD and normal subjects. IL-17 was produced by the ROS-producing populations E & F in all study groups, at increased levels compared to the NO-producing MDRC.…”

Section: Resultsmentioning

confidence: 99%

Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease

Deshane

Redden

Zeng

et al. 2015

Journal of Allergy and Clinical Immunology

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BACKGROUND Subsets of myeloid-derived regulatory cells (MDRC), phenotypically similar to myeloid-derived suppressor cells found in cancer, have recently been appreciated as critical regulators of airway inflammation in mouse models of asthma. OBJECTIVE We test the hypothesis that subsets of airway MDRC contribute differentially to the inflammatory milieu in human asthma and chronic obstructive pulmonary disease (COPD). METHODS We used BAL to identify and characterize human airway MDRC from 10 normal, 9 mild asthmatic and 8 COPD subjects, none treated with inhaled or systemic corticosteroids. We defined subsets of airway MDRC by flow cytometry, the molecular mediators they produce and their abilities to regulate proliferation of polyclonally activated autologous T-lymphocytes. RESULTS We found substantial differences in the functional potential of MDRC subsets in normal, asthmatic and COPD subjects, with these differences regulated by the nitrosative and oxidative free radicals and cytokines they produced. Nitric oxide-producing MDRC suppressed and superoxide-producing MDRC enhanced proliferation of polyclonally activated autologous CD4 T-cells. HLA-DR+CD11+CD11c+CD163− superoxide-producing MDRC, which stimulated proliferation of autologous T-cells, comprised a high fraction of MDRC in airways of subjects with mild asthma or COPD, but not normals. CD11b+CD14+CD16−HLA-DR− nitric oxide-producing MDRC, which suppressed T-cell proliferation, were present in high numbers in airways of subjects with mild asthma, but not subjects with COPD or normals. CONCLUSION Subsets of airway MDRC conclusively discriminate mild asthmatics, subjects with COPD and normal subjects from each other. The distinctive activities of these MDRC in asthma and COPD may provide novel targets for new therapeutics in these common disorders.

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Section: Resultsmentioning

confidence: 99%

Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease

Deshane

Redden

Zeng

et al. 2015

Journal of Allergy and Clinical Immunology

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“…Although many studies investigated the association between single nucleotide polymorphisms (SNP) in pro-inflammatory cytokine genes and asthma phenotypes (Che et al, 2014; Padron-Morales et al, 2013; Panek et al, 2014; Savenije et al, 2011; Zeyrek et al, 2008), there is only one study that focused on DA. Beghé et al (2004) studied tumor necrosis factor-α ( TNFα ) A-308G polymorphism in TDI-induced asthma but found no significant difference in frequency of this variant between cases and asymptomatic exposed subjects.…”

Section: Introductionmentioning

confidence: 99%

Genetic variants inTNFα,TGFB1, PTGS1andPTGS2genes are associated with diisocyanate-induced asthma

Yücesoy

Kashon

Johnson³

et al. 2015

Journal of Immunotoxicology

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Diisocyanates are the most common cause of occupational asthma, but risk factors are not well defined. A case-control study was conducted to investigate whether genetic variants in inflammatory response genes (TNFα, IL1α, IL1β, IL1RN, IL10, TGFB1, ADAM33, ALOX-5, PTGS1, PTGS2 and NAG-1/GDF15) are associated with increased susceptibility to diisocyanate asthma (DA). These genes were selected based on their role in asthmatic inflammatory processes and previously reported associations with asthma phenotypes. The main study population consisted of 237 Caucasian French Canadians from among a larger sample of 280 diisocyanate-exposed workers in two groups: workers with specific inhalation challenge (SIC) confirmed DA (DA+, n = 95) and asymptomatic exposed workers (AW, n = 142). Genotyping was performed on genomic DNA, using a 5′ nuclease PCR assay. After adjusting for potentially confounding variables of age, smoking status and duration of exposure, the PTGS1 rs5788 and TGFB1 rs1800469 single nucleotide polymorphisms (SNP) showed a protective effect under a dominant model (OR = 0.38; 95% CI = 0.17, 0.89 and OR = 0.38; 95% CI = 0.18, 0.74 respectively) while the TNFα rs1800629 SNP was associated with an increased risk of DA (OR = 2.08; 95% CI = 1.03, 4.17). Additionally, the PTGS2 rs20417 variant showed an association with increased risk of DA in a recessive genetic model (OR = 6.40; 95% CI = 1.06, 38.75).These results suggest that genetic variations in TNFα, TGFB1, PTGS1 and PTGS2 genes contribute to DA susceptibility.

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“…Furthermore, epithelial and monocytic cells (PBMCs and alveolar macrophages) taken from such patients respond to inflammatory stimuli with greater IL-1␤ production (21,48,68). Polymorphisms in IL-1␤ (also designated IL1B) and IL1ra (also designated IL1RN) are associated with a greater risk of COPD (34) and asthma (69), although the exact correlation remains to be clarified (2). Thus, evidence of the detrimental effects of IL-1␤ within the airway is established (60).…”

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confidence: 99%

Role of Interleukin-1 and MyD88-Dependent Signaling in Rhinovirus Infection

Stokes

Ismail

Dick

et al. 2011

J Virol

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Rhinoviral infection is an important trigger of acute inflammatory exacerbations in patients with underlying airway disease. We have previously established that interleukin-1␤ (IL-1␤) is central in the communication between epithelial cells and monocytes during the initiation of inflammation. In this study we explored the roles of IL-1␤ and its signaling pathways in the responses of airway cells to rhinovirus-1B (RV-1B) and further determined how responses to RV-1B were modified in a model of bacterial coinfection. Our results revealed that IL-1␤ dramatically potentiated RV-1B-induced proinflammatory responses, and while monocytes did not directly amplify responses to RV-1B alone, they played an important role in the responses observed with our coinfection model. MyD88 is the essential signaling adapter for IL-1␤ and most Toll-like receptors. To examine the role of MyD88 in more detail, we created stable MyD88 knockdown epithelial cells using short hairpin RNA (shRNA) targeted to MyD88. We determined that IL-1␤/MyD88 plays a role in regulating RV-1B replication and the inflammatory response to viral infection of airway cells. These results identify central roles for IL-1␤ and its signaling pathways in the production of CXCL8, a potent neutrophil chemoattractant, in viral infection. Thus, IL-1␤ is a viable target for controlling the neutrophilia that is often found in inflammatory airway disease and is exacerbated by viral infection of the airways.

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Association of interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in Turkish children with atopic asthma

Cited by 22 publications

References 22 publications

Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease

Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease

Genetic variants inTNFα,TGFB1, PTGS1andPTGS2genes are associated with diisocyanate-induced asthma

Role of Interleukin-1 and MyD88-Dependent Signaling in Rhinovirus Infection

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