Regulation of ferroptosis and ACSL4-15LO1 pathway contributed to the anti-asthma effect of acupuncture

Weifeng Tang; Jingjing Qin; Yaolong Zhou; Wenqian Wang; Fangzhou Teng; Jiaqi Liu; La Yi; Jie Cui; Xueyi Zhu; Shiyuan Wang; Jingcheng Dong; Ying Wei

doi:10.1016/j.intimp.2022.109670

Regulation of ferroptosis and ACSL4-15LO1 pathway contributed to the anti-asthma effect of acupuncture

Int Immunopharmacol. 2023 Feb:115:109670. doi: 10.1016/j.intimp.2022.109670. Epub 2023 Jan 4.

Authors

Affiliations

¹ Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China; Institutes of Integrative Medicine, Fudan University, Shanghai 200040, China.
² Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China; Institutes of Integrative Medicine, Fudan University, Shanghai 200040, China. Electronic address: jcdong2004@126.com.
³ Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China; Institutes of Integrative Medicine, Fudan University, Shanghai 200040, China. Electronic address: weiying_acup@126.com.

PMID: 36603356
DOI: 10.1016/j.intimp.2022.109670

Abstract

Acupuncture has been frequently used in China for the treatment asthma for thousands of years. Ferroptosis was recently revealed to be involved in several pathological conditions including asthma. However, the detailed links between ferroptosis and airway inflammation in asthma, as well as the detailed regulation of acupuncture on these disorders remains unclear. Our results demonstrated that the non-haem Fe²⁺ level increased markedly in the lung tissue of mouse asthma model, and positively correlated with R_L and IL-4 level in BALF. Furthermore, lipid peroxidation markers MDA and GSSG increased remarkably in OVA-induced experimental asthma mice. Up-regulation of lipid peroxidation associated proteins ACSL4 and15-LO1 was also observed in OVA-induced experimental asthma mice. To demonstrate the role of ferroptosis in asthma and the effect of acupuncture on these disorders, ferroptosis-induction agent erastin and ferroptosis-inhibition agent fer-1 were used, and our data demonstrated that erastin could augment lung inflammation and lipid peroxidation in OVA induced asthma model. Fer-1 was able to relieve AHR, lung inflammation, non-haem Fe²⁺ level, lipid peroxidation and ferroptosis related pathway ACSL4-15LO1 in OVA-induced experimental asthma mice. Acupuncture treatment alleviated R_L, lung inflammation as well as type 2 cytokines IL-4 and IL-13 levels induced by OVA inhalation. What's more, acupuncture significantly reduced the MDA and GSSG levels, the non-haem Fe²⁺ level and ACSL4-15-LO1 proteins expression. Acupuncture also relieved erastin-induced exacerbation in lung inflammation and lipid peroxidation in ferroptosis. Acupuncture treatment could relieve ferroptosis related exacerbation in airway inflammation. Our study provided insights into the underlying mechanisms for the protective effects of acupuncture and highlighted a therapeutic potential of acupuncture treatment in the attenuation of lipid peroxidation and ferroptosis in asthma.

Keywords: Acupuncture; Airway inflammation; Asthma; Ferroptosis; Lipid peroxidation.

MeSH terms

Acupuncture Therapy*
Animals
Anti-Asthmatic Agents* / pharmacology
Anti-Asthmatic Agents* / therapeutic use
Arachidonate 15-Lipoxygenase / metabolism
Asthma* / drug therapy
Asthma* / therapy
Coenzyme A Ligases / metabolism
Coenzyme A Ligases / pharmacology
Disease Models, Animal
Ferroptosis*
Glutathione Disulfide / adverse effects
Inflammation
Interleukin-4 / pharmacology
Mice
Ovalbumin / therapeutic use
Pneumonia* / drug therapy

Substances

Acsl4 protein, mouse
Anti-Asthmatic Agents
Coenzyme A Ligases
Glutathione Disulfide
Interleukin-4
Ovalbumin
Arachidonate 15-Lipoxygenase