4-Carvomenthenol ameliorates the murine combined allergic rhinitis and asthma syndrome by inhibiting IL-13 and mucus production via p38MAPK/NF-κB signaling pathway axis

Barros, Grasiela Costa Bezerra; Ferreira, Laércia Karla Diega Paiva; Ferreira, Larissa Adilis Maria Paiva; Monteiro, Talissa Mozzini; Alves, Adriano Francisco; Pereira, Ramon de Alencar; Piuvezam, Márcia Regina

doi:10.1016/j.intimp.2020.106938

Cited by 12 publications

(7 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AR is characterized by aberrantly high Th2 cytokines levels such as interleukin-4 (IL-4), IL-5, IL-6, and IL-13 ( Nur Husna et al, 2021a ). IL-4 and IL-13 are key pathogenic Th2 cytokines in AR where they activate B cells to synthesize IgE, induce goblet cell hyperplasia, trigger airway hyperresponsiveness, and mucus hypersecretion ( Wills-Karp and Finkelman, 2008 ; Sahoo et al, 2016 ; Bezerra Barros et al, 2020 ). IL-5 exerts pleiotropic effects on eosinophils by promoting their maturation, activation, survival, migration from bloodstream, and recruitment to airways in allergic disease ( Abo et al, 2019 ; Boberg et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

IL-4/IL-13 Axis in Allergic Rhinitis: Elevated Serum Cytokines Levels and Inverse Association With Tight Junction Molecules Expression

Husna

Shukri

Sharif

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

The IL-4/IL-13 axis is involved in the pathogenesis of allergic rhinitis (AR). In this study, we investigated the serum cytokines levels of IL-4, IL-5, IL-6, and IL-13 in AR patients, and the transcript expression levels of their receptors (i.e. IL4R, IL5RA, IL6R, and IL13RA1) in nasal epithelial cells of AR patients versus non-allergic controls. Nasal epithelial cells and blood samples of non-allergic controls (n = 30) and AR patients (n = 30) were collected to examine mRNA expression and serum cytokines levels, respectively. Bioinformatics analyses of IL-4/IL-13 receptor heterodimer association with tight junction (TJ) and JAK/STAT signaling genes were conducted in a gene expression profiling (GEP) dataset (GSE44037) of AR patients (n = 12) and healthy controls (n = 6). Serum IL-4, IL-5, IL-6 or IL-13 levels, and IL13RA1 transcript expression were significantly higher in AR patients compared with non-allergic controls. IL-4 and IL-13 serum levels were positively correlated with IL13RA1 expression in AR patients but not in non-allergic controls. In the GEP dataset (GSE44037), six TJ (CLDN4, CLDN7, CLDN12, CLDN15, TJP1, and TJP2) genes’ expressions were negatively correlated, respectively, with IL-4Rα/IL-13Rα1 heterodimeric receptor expression in AR patients and not in control samples. These six TJ genes contributed to the significant enrichment of tight junction Gene Ontology (GO ID: 0070160). Lastly, STATs DNA binding motif analysis showed that each of these TJ genes contains STATs binding consensus sequence within intronic and intergenic regions. Our results suggest that increased IL-4/IL-13 serum cytokines levels may contribute to decreased TJs expression via IL-4Rα/IL-13Rα1 heterodimeric receptor in nasal epithelium of AR patients.

show abstract

Section: Introductionmentioning

confidence: 99%

IL-4/IL-13 Axis in Allergic Rhinitis: Elevated Serum Cytokines Levels and Inverse Association With Tight Junction Molecules Expression

Husna

Shukri

Sharif

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…NF-кB pathway plays a key role in the regulation of inflammation in various cell types [37,38]. It has been suggested that the abnormal expression of miR-4454 is related to the activation of NF-кB, which can promote the development of various inflammatory diseases such as arthritis [39]. Other studies have demonstrated that CARAS airway inflammation is closely related to NF-кB pathway [40,41].…”

Section: Discussionmentioning

confidence: 99%

MiR-4454 in Combined Allergic Rhinitis and Asthma Syndrome (CARAS): Clinical significance and mechanistic insights into airway inflammation

Zhiguang Liu,

Chuang Sun,

Yujia Shi

et al. 2024

Cell Mol Biol (Noisy-le-grand)

View full text Add to dashboard Cite

Abnormal expression of non-coding microRNA is associated with the development of combined allergic rhinitis and asthma syndrome (CARAS). However, the function of miR-4454 in CARAS is unknown. Our study aimed to reveal the clinical significance and related mechanism of miR-4454 in CARAS. Blood samples from 38 cases of CARAS and 43 cases of healthy subjects were collected to detect the expression of miR-4454. House dust mite (HDM) sensitization and challenge-induced bronchial epithelial cells to simulate the asthma state model in vitro, miR-4454 mimics and inhibitor transfection to detect the expression level of pro-inflammatory cytokines, cell survival rate and migration ability, flow cytometry and western blot (WB) Detection of cell cycle, apoptosis and inflammation-related protein levels. Compared with healthy controls, the expression of miR-4454 in the blood of CARAS patients was significantly up-regulated, and IL-6 and IL-8 were significantly up-regulated in the HDM treatment group, indicating that the model induction was successful. After overexpression of miR-4454, cell proliferation and migration in the HDM-treated group were significantly inhibited, and the levels of early apoptosis and inflammation-related proteins (IL-17, IL-17RD, TNF-α, GCSF and NF-κB) were increased High; after inhibiting miR-4454, cell proliferation and migration were significantly enhanced, and the levels of apoptosis and inflammation-related proteins were decreased. This study found that inhibiting the expression of miR-4454 can improve HDM-induced cell injury, which may be related to miR-4454 regulating the activation of IL-17/NF-кB inflammatory axis.

show abstract

“…However, blocking NF-κB and p38MAPK with 4-carvomenthenol has been shown to improve combined allergic rhinitis and asthma syndrome. 98 In studies of rheumatoid arthritis (RA), the pathological cause is believed to be the presence of a large number of proinflammatory cytokines in synovial fluid. It is later considered that the combination and neutralization of TNF-α and IL-1 proinflammatory cytokines are very effective for the treatment of RA.…”

Section: Connection Between P38mapk and Inflammationmentioning

confidence: 99%

“…Phosphorylated p38MAPK coordinates the phosphorylation of MSK1, and directly phosphorylates nuclear factor‐kappa B (NF‐κB) to produce type 2 cytokines. However, blocking NF‐κB and p38MAPK with 4‐carvomenthenol has been shown to improve combined allergic rhinitis and asthma syndrome 98 …”

Section: Physiological Roles and Functions Of P38mapkmentioning

confidence: 99%

p38 mitogen‐activated protein kinase: Functions and targeted therapy in diseases

Zheng,

Li,

Wang

et al. 2023

MedComm – Oncology

View full text Add to dashboard Cite

P38 mitogen‐activated protein kinase (p38MAPK) is a multifunctional protein kinase that plays an important role in human normal physiological activities and a variety of major diseases, and its signaling pathway affects a variety of regulatory factors in vivo, which is related to cell cycle, survival, metabolism, and differentiation. The four subtypes of p38MAPK have significant differences in their distribution, content, and effects in the body. The inhibitors of the four subtypes play potential roles in regulating cancer, neurodegenerative diseases, inflammation, and cardiovascular diseases, making it an attractive target for drug development. So far, an increasing number of p38MAPK inhibitors have been developed for targeted therapy in diseases, among which some representative compounds have entered clinical trials. Therefore, this review aims to provide a summary of the structural characteristics, signaling pathways of P38MAPK and the relationship between p38MAPK and disease, along with an overview of the binding modes and structure–activity relationships of small molecule inhibitors targeting four p38MAPK subtypes, and summarizes the challenges about the development of p38MAPK inhibitors, hoping to provide a valuable reference for the development and application of novel inhibitors.

show abstract

4-Carvomenthenol ameliorates the murine combined allergic rhinitis and asthma syndrome by inhibiting IL-13 and mucus production via p38MAPK/NF-κB signaling pathway axis

Cited by 12 publications

References 31 publications

IL-4/IL-13 Axis in Allergic Rhinitis: Elevated Serum Cytokines Levels and Inverse Association With Tight Junction Molecules Expression

IL-4/IL-13 Axis in Allergic Rhinitis: Elevated Serum Cytokines Levels and Inverse Association With Tight Junction Molecules Expression

MiR-4454 in Combined Allergic Rhinitis and Asthma Syndrome (CARAS): Clinical significance and mechanistic insights into airway inflammation

p38 mitogen‐activated protein kinase: Functions and targeted therapy in diseases

Contact Info

Product

Resources

About