Interleukin-35 expression protects against cigarette smoke-induced lung inflammation in mice

Pan, X.; Xu, Keye; Li, Yuan; Wang, Xiaoying; Xiao, Peng; Li, Mingcai; Li, Yan

doi:10.1016/j.biopha.2018.12.028

Cited by 19 publications

(21 citation statements)

References 32 publications

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“…TNF-α, which is a marker of clinical severity and airflow limitation, is primarily secreted by macrophages. A previous report indicated that the expression of TNF-α was increased in pulmonary diseases (18), and the production of IL-6 was triggered by TNF-α. To investigate the effect of IL-35 on inflammation-associated signaling cascades, IL-35 was overexpressed in murine RAW264.7 macrophages.…”

Section: Discussionmentioning

confidence: 93%

Interleukin‑35 reduces inflammation in acute lung injury through inhibiting TLR4/NF‑κB signaling pathways

Pan

Wang³

et al. 2020

Exp Ther Med

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Acute lung injury (ALI) in children is a complex disease that is accompanied by an inflammatory response. The pathogenesis of ALI in children is not yet well understood. Mice with ALI exhibit inflammation of the lungs and decreased expression of interleukin (IL)-35. To investigate whether the function of IL-35 affects lipopolysaccharide (LPS)-induced ALI, IL-35 was overexpressed in cells. Enzyme-linked immunosorbent assays indicated decreased levels of IL-6 and tumor necrosis factor-α in LPS-induced and agomir-IL-35-treated murine RAW264.7 macrophages. Finally, toll-like receptor 4 (TLR4)/NF-κB signaling pathways were analyzed. The expression of TLR4, NF-κB p65 and NF-κB p50 were decreased, as was the degradation of NF-κB inhibitor-α, in LPS-induced and agomir-IL-35-treated murine RAW264.7 macrophages. The results of the present study demonstrated that IL-35 may exhibit a protective role in ALI by modulating the TLR4/NF-κB signaling pathways.

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Section: Discussionmentioning

confidence: 93%

Interleukin‑35 reduces inflammation in acute lung injury through inhibiting TLR4/NF‑κB signaling pathways

Pan

Wang³

et al. 2020

Exp Ther Med

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“…More importantly, the present study also indicated a positive correlation of the serum levels of IL‐1β with those of IL‐35 and IL‐37, indicating that pro‐inflammatory cytokines may also stimulate the expression of IL‐35 and IL‐37 under inflammatory conditions. In addition, previous studies have demonstrated that hydrodynamic injection of IL‐35 plasmid inhibited inflammatory cell infiltration in the lung, as well as mucus secretion and release of pro‐inflammatory cytokines IL‐1β, tumor necrosis factor‐α, IL‐6, and IL‐17 in the bronchoalveolar lavage fluid of mice exposed to cigarette smoke 33 . The present study also determined a positive correlation between IL‐35, IL‐37, and IL‐1β in patients with OSA, suggesting that IL‐35, IL‐37, and IL‐1β may interact in the pathogenesis of OSA.…”

Section: Discussionmentioning

confidence: 98%

“…A growing body of evidence indicates that IL‐37 is a novel anti‐inflammatory cytokine with broad anti‐inflammatory functions 30–33 . IL‐37 suppresses inflammation mainly by inhibiting the release of pro‐inflammatory cytokines by macrophages or epithelial cells and enhances anti‐inflammatory cytokine expression 34 .…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of interleukin‐35 and interleukin‐37 in adult patients with obstructive sleep apnea

Liu

et al. 2021

Clinical Laboratory Analysis

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Background Systemic inflammation has a critical role in the pathogenesis of obstructive sleep apnea (OSA). Interleukin (IL)‐35 and IL‐37 have been identified as novel immune‐modulating cytokines with anti‐inflammatory activities in numerous types of inflammatory disease. The present study aimed to examine the serum levels of IL‐35 and IL‐37 in patients with OSA, and to investigate their associations with the severity of OSA. Methods A total of 97 patients, including 67 cases of OSA and 30 age‐ and gender‐matched healthy control subjects, were enrolled in the present study. All subjects were evaluated by overnight polysomnography. Serum IL‐35, IL‐37, and pro‐inflammatory cytokine IL‐1β levels were examined by ELISA. Results Compared with those in the control subjects, serum IL‐35, IL‐37, and IL‐1β levels were significantly elevated in patients with mild, moderate, or severe OSA. Furthermore, a severity‐dependent increase in serum IL‐35 and IL‐37 levels was observed in patients with OSA. IL‐35 and IL‐37 levels were positively correlated with the apnea‐hypopnea index (r = 0.742 and 0.578, respectively; both p < 0.001), while they were negatively correlated with the mean oxygen saturation (r = −0.461 and −0.339, respectively; both p < 0.001) and lowest oxyhaemoglobin saturation (r = −0.616 and −0.463, respectively; both p < 0.001) in patients with OSA. In addition, a positive correlation was observed between IL‐35 or IL‐37 and IL‐1β levels (all p < 0.001). Conclusion The serum levels of IL‐35 and IL‐37 were significantly increased in patients with OSA and associated with the severity of OSA, implying that IL‐35 and IL‐37 may have a protective role in OSA by counteracting inflammatory responses.

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“…The function of IL-35 is complex and the results of different studies may be contradictory. IL-35 has a proinflammatory effect in certain diseases, such as rheumatoid arthritis [30,31] and Lyme arthritis [32], and has an anti-inflammatory effect in other diseases, such as liver inflammation [33], lung inflammation [34], airway inflammation [35], acquired aplastic anemia [36], atherosclerosis [37], arthritis [38], and colitis [39]. IL-35 also exerts different inflammatory effects in different models of the same disease.…”

Section: Discussionmentioning

confidence: 99%

Different expression levels of interleukin-35 in asthma phenotypes

Gao

Xin

et al. 2020

Respir Res

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Background: Interleukin (IL)-35 is a newly discovered inhibitory cytokine which is produced by regulatory B and T lymphocytes and belongs to the IL-12 family. It plays a suppressive role in human inflammatory diseases; however, its role in asthma phenotypes is unclear. Our study focuses on the sputum IL-35 level in patients and investigates different airway inflammation capacities of sputum IL-35 in patients with different asthma phenotypes. Objective: We aimed to determine the sputum IL-35 levels in asthmatic patients with clinical remission phenotypes and control subjects and to investigate possible correlations among lung function, age, sex, fractional exhaled nitric oxide (FeNO), and smoking history in these phenotypes. Methods: Sputum samples were collected from patients with clinical asthma remission (n = 89, 37 males, age 52.24 ± 13.32 years) and a healthy control group (n = 19, 9 males, age 44.58 ± 16.3 years). All subjects underwent sputum induction. Induced sputum was assessed for inflammatory cell count, and sputum levels of IL-35 and other cytokines were measured by ELISA and Cytometric Bead Array, respectively. Results: Sputum IL-35 (median (q1, q3)) levels showed no significant difference between asthma patients (4.89 ng/ mL (2.97, 22.75)) and healthy controls (6.01 ng/mL (4.09, 30.47)). However, the sputum IL-35 level was significantly reduced in patients with eosinophilic asthma (EA) (3.95 ng/mL (2.80, 11.00)) compared to patients with neutrophilic asthma (NA) (40.59 ng/mL (20.59, 65.06), p = 0.002), paucigranulocytic asthma (PA) (6.25 ng/mL (3.10, 24.60), p = 0.012), and mixed granulocytic asthma (MA) (22.54 ng/mL (2.58, 52.45), p = 0.026). IL-35 levels in sputum showed a positive correlation with sputum neutrophil cells and a negative correlation with FeNO, FEV1% predicted, and FVC predicted. Furthermore, sputum IL-35 had a significant positive association with Th1-related factors and a negative correlation with Th2-related factors. Conclusions: Sputum IL-35 is likely involved in different pathophysiological mechanisms of NA and EA and exerts different effects in asthma phenotypes.

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Interleukin-35 expression protects against cigarette smoke-induced lung inflammation in mice

Cited by 19 publications

References 32 publications

Interleukin‑35 reduces inflammation in acute lung injury through inhibiting TLR4/NF‑κB signaling pathways

Interleukin‑35 reduces inflammation in acute lung injury through inhibiting TLR4/NF‑κB signaling pathways

Elevated levels of interleukin‐35 and interleukin‐37 in adult patients with obstructive sleep apnea

Different expression levels of interleukin-35 in asthma phenotypes

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