<p>Erythromycin Prevents Elastin Peptide-Induced Emphysema and Modulates CD4⁺T Cell Responses in Mice</p>

Abstract

Elastin peptides (EP) can induce lung inflammation and emphysema. Erythromycin has been shown to decrease acute exacerbation frequency and delay lung function decline in chronic obstructive pulmonary disease patients and ameliorate emphysema in murine models; however, the mechanism remains unclear. We aimed to observe the preventive and immunomodulatory effects of erythromycin in a mouse model of EP-induced emphysema. Methods: In the in vivo study, Balb/c mice were treated with EP intranasally on day 0, and then administered erythromycin (100 mg/kg) or vehicle orally on day 1, which was continued every other day. Mice exposed to cigarette smoke were used as an emphysema positive control. The severity of emphysema and inflammation in the lungs of EP-exposed mice with or without erythromycin treatment were observed on day 40 after EP administration. In the in vitro study, naïve CD4 + T cells were isolated from healthy mice spleens and stimulated by EP with or without erythromycin incubation. Flow cytometry was used to measure the proportions of Th1, Th17, and Treg cells. ELISA was used to detect cytokine levels of IFN-γ, IL-17, IL-6, and TGF-β. Transcript levels of Ifnγ, IL17a, and Foxp3 were evaluated by qRT-PCR. Results: After exposure to EP, Th1 and Th17 cell percentages and the levels of inflammatory cytokines increased in vivo and in vitro, while Treg cells decreased in vivo. Erythromycin reduced IFN-γ, IL-17, IL-6 inflammatory cytokines, MLI, and the inflammation score in the lungs of EP-exposed mice. In vitro, erythromycin also limited Th17 and Th1 cell differentiation and downregulated transcript levels of Ifnγ and IL17a in the EPstimulated CD4 + T cells. Conclusion: The Th1 and Th17 cell responses were increased in EP-induced emphysema. Prophylactic use of erythromycin effectively ameliorated emphysema and modulated CD4 + T cells responses in EP-induced lung inflammation in mice.

RNA Sequencing and Related Differential Gene Expression Analysis in a Mouse Model of Emphysema Induced by Tobacco Smoke Combined with Elastin Peptides

“…The mean linear intercept (MLI) was used to assess alveolar airspace enlargement. 20 , 22 The MLI reflects the average alveolar diameter of mice and was compared with that of mice in the NORMAL group. All procedures were performed in a double-blind manner by two pathologists.…”

Th17/Treg Imbalance in Chronic Obstructive Pulmonary Disease: Clinical and Experimental Evidence

“…In accordance, mice that received elastin peptides (EP) intranasally, treatment with erythromycin was sufficient to reduce the IL-17 and IL-6 levels in both the serum and BALF compared to the EP group ( 72 ). Additionally, treatment with erythromycin modulated the CD4+ T cell responses by reducing the Th17 cells (IL-17+CD4 T+ frequency and IL-17 mRNA) and increasing the Treg response (FOXP3+CD4+ CD25+ frequency and Foxp3 mRNA) in the peripheral blood, spleen, and lungs ( 72 ). Additionally, Liu et al.…”

Regulatory T cells, damage-associated molecular patterns, and myeloid-derived suppressor cells in bronchoalveolar lavage fluid interlinked with chronic obstructive pulmonary disease severity

“…We also found a positive relationship between BALF Tregs and FEV1%pred and FVC% pred. Based on previous studies [54][55][56][57] conducted on mouse and rat models, a decrease in the percentage of Tregs promotes the development of emphysema. Our study results correspond to those mentioned above.…”