IL-1/inhibitory κB kinase ε–induced glycolysis augment epithelial effector function and promote allergic airways disease

Qian, Xi; Aboushousha, Reem; Wetering, Cheryl van de; Chia, Shi Biao; Amiel, Eyal; Schneider, Robert; Velden, Jos van der; Lahue, Karolyn G.; Hoagland, Daisy A.; Casey, D.; Daphtary, Nirav; Ather, Jennifer L.; Randall, Matthew J.; Aliyeva, Minara; Black, Kendall E.; Chapman, David G.; Lundblad, Lennart K. A.; McMillan, David H.; Dixon, Anne E.; Anathy, Vikas; Irvin, Charles G.; Poynter, Matthew E.; Wouters, Emiel F.M.; Vacek, Pamela M.; Henket, Monique; Schleich, Florence; Louis, Renaud; Vliet, Albert van der; Janssen–Heininger, Yvonne M. W.

doi:10.1016/j.jaci.2017.08.043

Cited by 46 publications

(60 citation statements)

References 64 publications

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“…Smallwood et al identified significant increases in glucose uptake in the lungs of pediatric patients infected with respiratory virus, and significant increases in glucose uptake and glycolytic flux occurring after influenza infection in primary human respiratory cells (13). In addition, elevated level of glycolysis and production of lactic acid were observed in asthmatic patients (17–19). Moreover, in the sputum of asthmatics the lactic acid level was positively correlated with sputum level of IL‐1β and negatively correlated with lung function of patients (18).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, elevated level of glycolysis and production of lactic acid were observed in asthmatic patients (17–19). Moreover, in the sputum of asthmatics the lactic acid level was positively correlated with sputum level of IL‐1β and negatively correlated with lung function of patients (18). Increased concentration of lactic acid may stimulate proliferating CD4 T cells, inhibition of glycolysis, and the increase of lactic acid attenuated airway inflammation and airway hyperreactivity in mouse model (18, 19).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, in the sputum of asthmatics the lactic acid level was positively correlated with sputum level of IL‐1β and negatively correlated with lung function of patients (18). Increased concentration of lactic acid may stimulate proliferating CD4 T cells, inhibition of glycolysis, and the increase of lactic acid attenuated airway inflammation and airway hyperreactivity in mouse model (18, 19). In this current study, we observed that serum level of L‐lactic acid was positively associated with levels of serum CXCL8.…”

Section: Discussionmentioning

confidence: 99%

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Serum metabolomic profiling reveals important difference between infants with and without subsequent recurrent wheezing in later childhood after RSV bronchiolitis

Zhang

Peng

Zhang

et al. 2020

APMIS

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We aimed to use serum metabolomics to discriminate infants with severe respiratory syncytial virus (RSV) bronchiolitis who later developed subsequent recurrent wheezing from those who did not and to investigate the relationship between serum metabolome and host immune responses with regard to the subsequent development of recurrent wheezing. Fifty‐one infants who were hospitalized during an initial episode of severe RSV bronchiolitis at 6 months of age or less were included and followed for up to the age of 3 years. Of them, 24 developed subsequent recurrent wheezing and 27 did not. Untargeted serum metabolomics was performed by ultraperformance liquid chromatography coupled with high‐resolution mass spectrometry (UPLC‐MS/MS). Cytokines were measured by multiplex immunoassay. Difference in serum metabolomic profiles was observed between infants who developed recurrent wheezing and those who did not. L‐lactic acid level was significantly higher in infants with recurrent wheezing than those without. Pyrimidine metabolism, glycerophospholipid metabolism, and arginine biosynthesis were identified as the most significant changed pathways between the two groups. Moreover, L‐lactic acid level was positively associated with serum CXCL8 level. This exploratory study showed that differential serum metabolic signatures during severe RSV bronchiolitis in early infancy were associated with the development of subsequent recurrent wheezing in later childhood.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Serum metabolomic profiling reveals important difference between infants with and without subsequent recurrent wheezing in later childhood after RSV bronchiolitis

Zhang

Peng

Zhang

et al. 2020

APMIS

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“…Energy metabolic pathway switch in asthmatic patients. Prior studies have shown that asthmatic patients had elevated serum and sputum levels of lactate and that cell from asthmatic patients produced higher amounts of lactate upon stimulation 28,29 . OVA sensitization and challenge upregulated glycolysis enzyme expression in rat lungs 30 .…”

Section: Resultsmentioning

confidence: 99%

“…Prior studies have reported that asthmatic patients had elevated serum and sputum levels of lactate and that cell from asthmatic patients produced higher amounts of lactate upon stimulation 28,29 , suggesting an enhanced glycolysis. However, these prior studies did not address the question whether the enhanced glycolysis is accompanied by a repressed OXPHOS activity (whether an energy metabolic pathway switch occurs).…”

Section: Discussionmentioning

confidence: 95%

Hydrogen Attenuates Allergic Inflammation by Reversing Energy Metabolic Pathway Switch

Niu

Nie

Dong

et al. 2020

Sci Rep

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Mechanisms mediating the protective effects of molecular hydrogen (H 2) are not well understood. This study explored the possibility that H 2 exerts its anti-inflammatory effect by modulating energy metabolic pathway switch. Activities of glycolytic and mitochondrial oxidative phosphorylation systems were assessed in asthmatic patients and in mouse model of allergic airway inflammation. The effects of hydrogen treatment on airway inflammation and on changes in activities of these two pathways were evaluated. Monocytes from asthmatic patients and lungs from ovalbumin-sensitized and challenged mice had increased lactate production and glycolytic enzyme activities (enhanced glycolysis), accompanied by decreased ATP production and mitochondrial respiratory chain complex I and III activities (suppressed mitochondrial oxidative phosphorylation), indicating an energy metabolic pathway switch. Treatment of ovalbumin-sensitized and challenged mice with hydrogen reversed the energy metabolic pathway switch, and mitigated airway inflammation. Hydrogen abrogated ovalbumin sensitization and challenge-induced upregulation of glycolytic enzymes and hypoxiainducible factor-1α, and downregulation of mitochondrial respiratory chain complexes and peroxisome proliferator activated receptor-γ coactivator-1α. Hydrogen abrogated ovalbumin sensitization and challenge-induced sirtuins 1, 3, 5 and 6 downregulation. Our data demonstrates that allergic airway inflammation is associated with an energy metabolic pathway switch from oxidative phosphorylation to aerobic glycolysis. Hydrogen inhibits airway inflammation by reversing this switch. Hydrogen regulates energy metabolic reprogramming by acting at multiple levels in the energy metabolism regulation pathways.

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Obesity and Asthma: Metabolic Dysregulation

Holguin

2024

Respiratory Medicine

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IL-1/inhibitory κB kinase ε–induced glycolysis augment epithelial effector function and promote allergic airways disease

Abstract: Collectively, these findings demonstrate that IL-1β/inhibitory κB kinase ε signaling plays an important role in HDM-induced glycolysis and pathogenesis of allergic airways disease.

Cited by 46 publications

References 64 publications

Serum metabolomic profiling reveals important difference between infants with and without subsequent recurrent wheezing in later childhood after RSV bronchiolitis

Serum metabolomic profiling reveals important difference between infants with and without subsequent recurrent wheezing in later childhood after RSV bronchiolitis

Hydrogen Attenuates Allergic Inflammation by Reversing Energy Metabolic Pathway Switch

Obesity and Asthma: Metabolic Dysregulation

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