Restoring Th17/Treg balance via modulation of STAT3 and STAT5 activation contributes to the amelioration of chronic obstructive pulmonary disease by Bufei Yishen formula

Abstract

Ethnopharmacology relevance: Bufei Yishen formula (BYF), a Traditional Chinese Medicine (TCM), has been extensively applied in clinical treatment of chronic obstructive pulmonary disease (COPD) and provides an effective treatment strategy for the syndrome of lung-kidney qi deficiency in COPD patients. Here, we investigated its anti-COPD mechanism in COPD rats in relation to the balance between T helper (Th) 17 cells and regulatory T (Treg) cells.

Methods: Rat model of cigarette smoke- and bacterial infection-induced COPD was established, and orally treated with BYF for 12 consecutive weeks. Then, the rats were sacrificed, their lung tissues were removed for histological analysis, and spleens and mesenteric lymph nodes (MLNs) were collected to evaluate the Th17 and Treg cells.

Results: Oral treatment of BYF markedly suppressed the disease progression and alleviated the pathological changes of COPD. It also decreased the bronchoalveolar lavage fluid (BALF) levels of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α and Th17-related IL-17A, and induced a significant increase in Treg-related IL-10. Furthermore, BYF treatment obviously decreased the proportion of CD4⁺RORγt⁺ T (Th17) cell and increased the proportion of CD4⁺CD25⁺Foxp3⁺ T (Treg) cell, leading to restore the Th17/Treg balance. BYF treated groups also decreased RORγt and increased Foxp3 expression in the spleens and MLNs. BYF further inhibited the phosphorylation of signal transducer and activator of transcription-3 (STAT3) and boosted the phosphorylation of STAT5, that were critical transcription factors for TH17 and Treg differentiation.

Conclusion: these results demonstrated that BYF exerted its anti-COPD efficacy by restoring Th17/Treg balance via reciprocally modulating the activities of STAT3 and STAT5 in COPD rats, which may help to elucidate the underlying immunomodulatory mode of BYF on COPD treatment.

Keywords: 3,3′-diaminobenzidine (PubChem CID:7071); Bufei Yishen formula; Chronic obstructive pulmonary disease; Ethanol (PubChem CID: 702); Formaldehyde (PubChem CID: 712); Formalin (PubChem CID: 712); Phosphate-buffered saline (PubChem CID: 24978514); Regulatory T cells; STAT3; STAT5; Sodium dodecyl sulfate (PubChem CID: 3423265); T helper 17 cells; Thiobarbituric acid (PubChem CID: 2723628); Xylene (PubChem CID: 7237).