MHTP, a synthetic alkaloid, attenuates combined allergic rhinitis and asthma syndrome through downregulation of the p38/ERK1/2 MAPK signaling pathway in mice

Ferreira, Laércia Karla Diega Paiva; Ferreira, Larissa Adilis Maria Paiva; Barros, Grasiela Costa Bezerra; Monteiro, Talissa Mozzini; Silva, Luiz A. de Araújo; Pereira, Ramon de Alencar; Figueiredo, Pedro Thiago Ramalho de; Alves, Adriano Francisco; Rodrigues, Luís Cézar; Piuvezam, Márcia Regina

doi:10.1016/j.intimp.2021.107590

Cited by 14 publications

(8 citation statements)

References 37 publications

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“…It is reported that activation of the MAPK pathway and JNK pathway positively affect allergic rhinitis. 32,33 In this study, we examine the gene expression of the nasal mucosa through RNA-seq. We found that the regulation of JNK activity pathway and activation of MAPKK activity pathway were significantly upregulated in the C57BL/6 mice compared to the BALB/c mice.…”

Section: Discussionmentioning

confidence: 99%

A Preliminary Study in Immune Response of BALB/c and C57BL/6 Mice with a Locally Allergic Rhinitis Model

Zhang

Zhu

Zou

et al. 2023

Am J Rhinol�Allergy

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Background BALB/c and C57BL/6 mouse strains are commonly used in allergy research. The current study investigated the immunological differences between these two mouse strains with a locally allergic rhinitis model. Methods Eighteen BALB/c and eighteen C57BL/6 mice received different doses of ovalbumin (OVA) intranasally for eight weeks (each mouse strain has three subgroups, 25 mg/mL group, 0.25 mg/mL group, and the PBS group). The allergic symptoms, OVA-specific serum antibody (IgE, IgG1, IgG2a), cytokines (IL-4, IFN-γ, IL-10) in the splenic culture supernatant, infiltrating eosinophils and goblet cells in local nasal mucosa were measured. RNA-seq technology was applied to detect differential gene expression in the local nasal mucosa. Results With the same dose of OVA stimulation, the exacerbation of allergic symptoms was more pronounced in C57BL/6 than in BALB/c. BALB/c serum IgE, IgG1, and IgG2a gradually increased, and C57BL/6 produced fewer serum antibodies IgE and IgG1, while IgG2a never increased. BALB/c spleen cell culture supernatant IL-4 and IL-10 increased with increasing dose, and IFN-γ increased significantly in the intermediate dose group, while IL-4, IL-10, and IFN-γ did not increase in C57BL/6. The infiltration of eosinophils and goblet cells in both mice was proportional to the dose, while C57BL/6 was elevated more than BALB/c. RNA-seq suggested that the innate immune response, immune system process function, Jun kinase (JNK) pathway, and MAPKK pathway were upregulated in C57BL/6 compared to BALB/c. The core genes responsible for the differential immune response in both mice with allergic rhinitis were Kng2, Kng1, Gnb3, Lpar3, Lpar1, Pik3r1, Pf4, Apob, Rps9, and Fbxo2. Conclusion There are significant differences in the immunologic responses between BALB/c mice and C57BL/6 mice. BALB/c mice developed mild local allergic inflammatory reactions and strong systemic immune responses. In contrast, C57BL/6 mice had stronger local allergic inflammatory responses and relatively mild systemic immune responses. Different mice strains can be selected according to the research purpose.

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Section: Discussionmentioning

confidence: 99%

A Preliminary Study in Immune Response of BALB/c and C57BL/6 Mice with a Locally Allergic Rhinitis Model

Zhang

Zhu

Zou

et al. 2023

Am J Rhinol�Allergy

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“…First, the samples from AR patients and healthy controls were too small. Second, some signaling pathways, such as IL‐33/ST2 signaling, 38 the NF‐κB pathway, 20 and the p38/ERK1/2 MAPK pathway, 39 have been reported to participate in AR development. Thus, whether the miR‐214‐3p/GSK3B axis can regulate these signaling pathways in AR should be investigated in future studies.…”

Section: Discussionmentioning

confidence: 99%

“…First, the samples from AR patients and healthy controls were too small. Second, some signaling pathways, such as IL-33/ST2 signaling, 38 the NF-κB pathway, 20 and the p38/ERK1/2 MAPK pathway, 39 have been reported to participate in AR development.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐214‐3p facilitates M2 macrophage polarization by targeting GSK3B

Peng

Deng

et al. 2022

The Kaohsiung J of Med Scie

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Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa. M2 macrophage polarization can reduce inflammation and repair tissue injury during AR development. Studies have substantiated the involvement of miRNAs in AR pathogenesis. Herein, the molecular mechanism of miR‐214‐3p in AR development was explored. To mimic the AR environment, ovalbumin (OVA) was used to treat macrophages. MiR‐214‐3p and glycogen synthase kinase 3 beta (GSK3B) expression in nasal mucus tissues and macrophages was assessed by RT‐qPCR. The M2 phenotypic signature of CD206 in macrophages was assessed by flow cytometry. The protein expression of GSK3B and M2 macrophage markers (ARG‐1 and IL‐10) was evaluated by western blotting. The correlation between miR‐214‐3p and GSK3B was validated by a luciferase reporter assay. We found that miR‐214‐3p was overexpressed in macrophages and nasal mucus tissues from AR patients. MiR‐214‐3p facilitated M2 polarization of macrophages upon OVA stimulation. Mechanistically, miR‐214‐3p targeted the GSK3B 3′ untranslated region in macrophages. In addition, GSK3B was downregulated in macrophages and nasal mucus tissues from AR patients. In rescue assays, GSK3B downregulation reversed the inhibitory effects of miR‐214‐3p silencing on M2 polarization of macrophages treated with OVA. Overall, miR‐214‐3p facilitates M2 macrophage polarization by targeting GSK3B.

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“…MAPK and JAK/STAT signaling pathways play key roles in the proliferation, differentiation, and production of inflammatory cells and are involved in the activation of AR ( Yang et al, 2021 ). After blocking the MAPK or JAK/STAT signaling pathways, the symptoms of rhinitis in AR mice were reduced, and the aggregation of inflammatory cells in the epithelial cells of the nasal mucosa and vascular area was decreased ( Howell et al, 2018 ; Paiva Ferreira et al, 2021 ). These observations show that the pathways play important roles in AR regulation, and indicate the reliability of the 140 selected AR/YPFS-related genes.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology analysis and experimental verification reveal the mechanism of the traditional Chinese medicine YU-Pingfeng San alleviating allergic rhinitis inflammatory responses

et al. 2022

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YU-Pingfeng San (YPFS) can regulate inflammatory response to alleviate the symptoms of nasal congestion and runny rose in allergic rhinitis (AR). However, the mechanism of action remains unclear. In this study, 30 active ingredients of three effective herbs included in YPFS and 140 AR/YPFS-related genes were identified by database analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the targets were mainly enriched in immune inflammatory-related biological processes and pathways. Finally, three hub gene targeting epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), and protein kinase B1 (AKT1) related to YPFS and AR were identified by network pharmacology analysis. YPFS treatment decreased the expression of EGFR, MAPK1, and AKT1 in ovalbumin (OVA)-induced AR mice and impaired the production of inflammatory factors interleukin (IL)-4, IL-5, and IL-13, thus alleviating immunoglobulin E (IgE) production and the symptoms of scratching nose in AR. Through molecular docking analysis, we found that the active ingredients decursin, anomalin, and wogonin of YPFS could bind to EGFR, MAPK1, and AKT1 proteins. Moreover, decursin treatment impaired the expression of IL-4 and IL-5 in human PBMCs. These results suggested that YPFS could alleviate the AR inflammatory responses by targeting EGFR, MAPK1, and AKT1, showing the mechanism of action of YPFS in AR treatment.

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MHTP, a synthetic alkaloid, attenuates combined allergic rhinitis and asthma syndrome through downregulation of the p38/ERK1/2 MAPK signaling pathway in mice

Cited by 14 publications

References 37 publications

A Preliminary Study in Immune Response of BALB/c and C57BL/6 Mice with a Locally Allergic Rhinitis Model

A Preliminary Study in Immune Response of BALB/c and C57BL/6 Mice with a Locally Allergic Rhinitis Model

MicroRNA‐214‐3p facilitates M2 macrophage polarization by targeting GSK3B

Network pharmacology analysis and experimental verification reveal the mechanism of the traditional Chinese medicine YU-Pingfeng San alleviating allergic rhinitis inflammatory responses

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