Codonopsis lanceolata attenuates allergic lung inflammation by inhibiting Th2 cell activation and augmenting mitochondrial ROS dismutase (SOD2) expression

Yun-Soo Seo,Jin Mi Chun,Sung Bae Kim,Bo-In Kwon,Hyo Seon Kim,A Yeong Lee,Byeong Cheol Moon

doi:10.1038/s41598-019-38782-6

Yun-Soo Seo, Jin Mi Chun + Show 5 more

Open Access

https://doi.org/10.1038/s41598-019-38782-6

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Abstract

Allergic asthma is a chronic inflammatory disease induced by the inhalation of allergens, which trigger the activation of T helper type 2 (Th2) cells that release Th2 cytokines. Recently, herbal medicines are being considered a major source of novel agents to treat various diseases. In the present study, we evaluated the anti-asthmatic effects of a Codonopsis lanceolata extract (CLE) and the mechanisms involved in its anti-inflammatory effects. Treatment with CLE reduced infiltration of inflammatory cells, especially eosinophils, and the production of mucus in lung tissues. Levels of Th2 cytokines, such as IL-4, IL-5, and IL-13, and chemokines were also decreased following treatment with CLE. Moreover, Th2 cell proportion in vivo and differentiation in vitro were reduced as evidenced by the decreased expression of GATA3+. Furthermore, the expression of superoxide dismutase (SOD)2, a mitochondrial ROS (mROS) scavenger, was increased, which was related to Th2 cell regulation. Interestingly, treatment with CLE increased the number of macrophages in the lungs and enhanced the immune-suppressive property of macrophages. Our findings indicate that CLE has potential as a novel therapeutic agent to inhibit Th2 cell differentiation by regulating mROS scavenging.

Highlights

Allergic asthma is a chronic pulmonary disease caused by an inappropriate immune response to aeroallergens in susceptible individuals
The pathogenesis of OVA-induced asthma is characterised by allergen-activated secretion of Th2 cell cytokines, which induce IgE production, influx of inflammatory cells, such as eosinophils, into the lungs, mucus hyper-production, and airway hyper-responsiveness (AHR)[42]
The dried roots of C. lanceolata have been used for the treatment of inflammatory diseases of the respiratory system such as asthma, tonsillitis, and pharyngitis

Summary

Introduction

Allergic asthma is a chronic pulmonary disease caused by an inappropriate immune response to aeroallergens in susceptible individuals. Allergic asthma is characterised by several clinical symptoms, including airway hyper-responsiveness, mucus hypersecretion, and inflammatory cell infiltration, induced by the inhalation of allergens such as pollen, house dust, inhalants, and air pollutants[1]. The allergens processed by antigen-presenting cells trigger the activation of T helper type 2 (Th2) cells that release Th2 cytokines, which induce inflammatory cell infiltration into the airways[2,3]. Macrophages, which are the most abundant immune cells in the lungs, link the innate and adaptive immune systems during allergen-induced airway inflammation. Macrophages localised to the interstitial area of the lung appear to be less prone to polarisation toward either the M1 or the M2a phenotype, as these cells predominately express IL-10 and exhibit immunosuppressive properties similar to the M2c phenotype[19]. Polarisation of macrophages depends on various environmental stimuli: deficiency in ROS production induces polarisation toward the M2 phenotype followed by a reduction in TNFα and IL-1β levels[20]; and deficiency in SOD levels induces an increase in alveolar macrophages with the M1 phenotype[21]

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