Interleukin-37 alleviates airway inflammation and remodeling in asthma via inhibiting the activation of NF-κB and STAT3 signalings

Huang, Nina; Liu, Kebei; Liu, Jianping; Gao, Xiaopeng; Zeng, Zhu; Zhang, Yudan; Chen, Jing

doi:10.1016/j.intimp.2017.12.010

Cited by 55 publications

(31 citation statements)

References 36 publications

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“…Myofibroblasts express α-SMA, which mediate the contractile activity of fibroblastic cells, in addition to their production of collagen types I, III, IV and V [97]. Moreover, TGF-β1 increases contractility, migration and proliferation of airway smooth muscle cells [95,98]. Therefore, it is not surprising that TGF-β1 correlates with the airway narrowing and limitation of air movements in asthmatic patients [91].…”

Section: Tgf-β1mentioning

confidence: 99%

Alternatively activated macrophages; a double-edged sword in allergic asthma

et al. 2020

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Background: Macrophages are heterogenous phagocytic cells with an important role in the innate immunity. They are, also, significant contributors in the adaptive immune system. Macrophages are the most abundant immune cells in the lung during allergic asthma, which is the most common chronic respiratory disease of both adults and children. Macrophages activated by Th1 cells are known as M1 macrophages while those activated by IL-4 and IL-13 are called alternatively activated macrophages (AAM) or M2 cells. AAM are subdivided into four distinct subtypes (M2a, M2b, M2c and M2d), depending on the nature of inducing agent and the expressed markers. Body: IL-4 is the major effector cytokine in both alternative activation of macrophages and pathogenesis of asthma. Thus, the role of M2a macrophages in asthma is a major concern. However, this is controversial. Therefore, further studies are required to improve our knowledge about the role of IL-4-induced macrophages in allergic asthma, through precisive elucidation of the roles of specific M2a proteins in the pathogenesis of asthma. In the current review, we try to illustrate the different functions of M2a macrophages (protective and pathogenic roles) in the pathogenesis of asthma, including explanation of how different M2a proteins and markers act during the pathogenesis of allergic asthma. These include surface markers, enzymes, secreted proteins, chemokines, cytokines, signal transduction proteins and transcription factors. Conclusions: AAM is considered a double-edged sword in allergic asthma. Finally, we recommend further studies that focus on increased selective expression or suppression of protective and pathogenic M2a markers.

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Section: Tgf-β1mentioning

confidence: 99%

Alternatively activated macrophages; a double-edged sword in allergic asthma

et al. 2020

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“…Higher level of activated NF-κB is observed in asthma, various strategies targeting NF-κB signaling have been considered for asthma treatment [22]. STAT3 is an important transcription factor that has been found to be implicated in airway inflammation and remodeling in asthma [23]. Jeon et al [8] reported that eupatilin inhibits NF-κB signaling in bronchial epithelial cells, leading to inhibition of eosinophil migration.…”

Section: Discussionmentioning

confidence: 99%

Eupatilin alleviates airway remodeling via regulating phenotype plasticity of airway smooth muscle cells

Ren

Wang

et al. 2020

Bioscience Reports

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Childhood asthma is a common chronic airway disease, and its severe form remains a challenge. Eupatilin is a bioactive natural flavone that has been found to possess potential anti-asthma activity. However, the roles of eupatilin in asthma remain to be elucidated. In the present study, airway smooth muscle cells (ASMCs) were applied for the in vitro investigation since their phenotype plasticity make great contribution to airway remodeling during asthma pathogenesis. Our results showed that eupatilin suppressed the transforming growth factor β1 (TGF-β1)-induced proliferation and migration of ASMCs. Exposure of ASMCs to eupatilin increased the expressions of contractile markers smooth muscle α-actin (α-SMA) and myocardin, whereas expressions of extracellular matrix (ECM) proteins type I collagen (Coll I) and fibronectin were reduced. Furthermore, eupatilin treatment reversed the activation of nuclear factor-κ B (NF-κB), signal transducer and activator of transcription 3 (STAT3) and AKT pathways caused by TGF-β1 in ASMCs. These findings suggested that eupatilin might attenuate airway remodeling via regulating phenotype plasticity of ASMCs.

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“…The levels of in ammation and brosis in the STAT3-siRNA group were signi cantly reduced compared with that in the RHD group. STAT3 is also involved in many diseases, such as airway in ammation and rheumatoid arthritis [32][33][34][35]. The persistent activation and high expression of STAT3 in tumour cells promotes tumour growth and proliferation [7].…”

Section: Discussionmentioning

confidence: 99%

The intervention of S1PR1/STAT3 signaling pathway by inhibiting the expression of STAT3 attenuates the valvular damage due to rheumatic heart disease

Xian¹,

Chen²,

Yi-ming³

et al. 2020

Preprint

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Background Rheumatic heart disease (RHD) is a social health problem that affects many patients every year, but its pathogenesis is still unclear. Recent studies have found that the sphingosine 1-phosphate receptor 1 (S1PR1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is activated during the development of valvular damage caused by RHD. STAT3 plays an important role in the differentiation of CD4 + T cells into T helper 17 (Th17) cells, and Th17 cell-related cytokines are involved in the development of RHD. In this work, we investigated whether altering the S1PR1/STAT3 signaling pathway by inhibiting the expression of STAT3 attenuates valvular damage due to RHD. Methods Inactivated Group A streptococci (GAS) and complete Freund’s adjuvant (CFA) were used to establish the RHD rat model. STAT3-small interfering RNA (STAT3-siRNA) was used to directly inhibit the expression of STAT3 in the heart. Histological examination was used to evaluate the degree of inflammation and fibrosis in valve tissues. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the levels of interleukin (IL)-6 and IL-17 in serum and valve tissue. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect the mRNA expression of S1PR1 and STAT3. Western blotting (WB) and immunohistochemistry were used to detect the protein expression of S1PR1, STAT3, phosphorylated (p-) STAT3, retinoic acid-related orphan receptor gamma T (RORγt). Results The expression of S1PR1 in valve tissues of RHD model rats was decreased. The degree of valvular inflammation and fibrosis of RHD model rats was increased. The levels of IL-6 and IL-17 in valves and serum of RHD model rats were increased as well as an increase of p-STAT3 in valve tissues. Inhibition of STAT3 by STAT3-siRNA decreased STAT3 expression and reduced the total amount of p-STAT3, resulting in decreased expression of IL-6, IL-17 and RORγt in valves and serum and reduced valvular inflammatory response and fibrosis. Conclusions These results suggest that inhibiting the expression of STAT3 in the heart may reduce the valvular damage caused by rheumatic heart disease.

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Interleukin-37 alleviates airway inflammation and remodeling in asthma via inhibiting the activation of NF-κB and STAT3 signalings

Cited by 55 publications

References 36 publications

Alternatively activated macrophages; a double-edged sword in allergic asthma

Alternatively activated macrophages; a double-edged sword in allergic asthma

Eupatilin alleviates airway remodeling via regulating phenotype plasticity of airway smooth muscle cells

The intervention of S1PR1/STAT3 signaling pathway by inhibiting the expression of STAT3 attenuates the valvular damage due to rheumatic heart disease

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