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. 2021 Dec;12(1):5279-5288.
doi: 10.1080/21655979.2021.1964158.

Interleukin-6 promotes ferroptosis in bronchial epithelial cells by inducing reactive oxygen species-dependent lipid peroxidation and disrupting iron homeostasis

Fei Han  1   2   3 , Shijie Li  1   2   3 , Yankun Yang  1   2   3 , Zhonghu Bai  1   2   3
Affiliations

Interleukin-6 promotes ferroptosis in bronchial epithelial cells by inducing reactive oxygen species-dependent lipid peroxidation and disrupting iron homeostasis

Fei Han et al. Bioengineered. 2021 Dec.

Abstract

Asthma occurs accompanied by the ferroptosis in bronchial epithelial cells, during which Interleukin-6 (IL-6) plays a key role. However, the associations between IL-6, ferroptosis and asthma have not been reported. Bronchial epithelial cells BEAS-2B cells were induced by different concentrations of IL-6 and cell viability was detected by MTT assay. The TBARS production rate was detected by corresponding kit. The expression of oxidative stress-related indexes was detected by ELISA. The Iron Assay Kits detected total iron levels and ferrous ion (Fe2+) levels. Labile iron pool assay was used to detect the cell unstable iron pool. The expression of ferroptosis-related proteins was detected by Western blot. To further examine the mechanism of action, ferroptosis inhibitor Ferrostatin 1 (Fer-1), antioxidant NAC, and the iron supplement Fe were added. We found that IL-6 decreased the activity, promoted lipid peroxidation, disrupted iron homeostasis of BEAS-2B cells, and induced iron death in bronchial epithelial BEAS-2B cells. However, pretreatment with Ferrostatin-1 (Fer-1) and antioxidant NAC partially reversed the effect of IL-6 on lipid peroxidation and ferroptosis in BEAS-2B cells, while Fe augmented the effect. Overall, IL-6 promotes ferroptosis in bronchial epithelial cells by inducing reactive oxygen species (ROS)-dependent lipid peroxidation and disrupting iron homeostasis.

Keywords: IL-6; asthma; bronchial epithelial cells; ferroptosis; iron homeostasis; lipid peroxidation.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
IL-6 decreased the activity and promoted lipid peroxidation of BEAS-2B cells. A. MTT assay detected the cell viability. B. The TBARS production rate was determined by the kit. C. The corresponding kits were used to detect the expression of the indexes related to oxidative stress. *p < 0.05, **p < 0.01, ***p < 0.001 vs Control
Figure 2.
Figure 2.
IL-6 disrupted iron homeostasis and induced ferroptosis of BEAS-2B cells. A. Iron Assay Kit detected total iron levels in cells. B. Iron Assay Kit detected Fe2+ levels in cells. C. LIP Assay was used to detect the iron expression. D. Western blot detected the expression of ferroptosis-related proteins. *p < 0.05, **p < 0.01, ***p < 0.001 vs Control
Figure 3.
Figure 3.
Pretreatment with Fer-1 and NAC partially reversed the effect of IL-6 on lipid peroxidation in BEAS-2B cells, while Fe increased those effects. A. MTT assay detected the cell viability after the induction of Fer-1, Fe and NAC. B. The TBARS production rate was determined by the kit after the induction of Fer-1, Fe and NAC. C. The corresponding kits were used to detect the expression of the indexes related to oxidative stress after the induction of Fer-1, Fe and NAC. ***p < 0.001 vs Control; #p < 0.05, ###p < 0.001 vs IL-6
Figure 4.
Figure 4.
Pretreatment with Fer-1 and NAC partially reversed the effect of IL-6 on ferroptosis in BEAS-2B cells, while Fe increased those effects. A. Iron Assay Kit detected total iron levels in cells after the induction of Fer-1, Fe and NAC. B. Iron Assay Kit detected Fe2+ levels in cells after the induction of Fer-1, Fe and NAC. C. LIP Assay was used to detect the iron expression after the induction of Fer-1, Fe and NAC. D. Western blot detected the expression of ferroptosis-related proteins after the induction of Fer-1, Fe and NAC. ***p < 0.001 vs Control; #p < 0.05, ##p < 0.01, ###p < 0.001 vs IL-6
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