2. Academic Validation
  3. HO-1 relied on PI3K/mTOR signaling to alleviate inflammation by reducing the apoptosis and autophagy of bovine mammary epithelial cells

HO-1 relied on PI3K/mTOR signaling to alleviate inflammation by reducing the apoptosis and autophagy of bovine mammary epithelial cells

  • Int Immunopharmacol. 2026 May 15:177:116545. doi: 10.1016/j.intimp.2026.116545.
Yueying Wang 1,  Xinyi Zhang 1,  Shuhui Xu 1,  Junxian Jing 1,  Xiaoxiao Liu 1,  Qilong Yang 1,  Dai Peng 1,  Linlin Huang 1,  Shiang Sun 1,  Yang Liu 2,  Heping Li 3,  Yingqian Han 4
Affiliations

Affiliations

  • 1 Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan, China.; Key Laboratory of Veterinary Biotechnology of Henan Province, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan, China.
  • 2 Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan, China.; Key Laboratory of Veterinary Biotechnology of Henan Province, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan, China.. Electronic address: [email protected].
  • 3 Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan, China.; Key Laboratory of Veterinary Biotechnology of Henan Province, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan, China.. Electronic address: [email protected].
  • 4 Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan, China.; Key Laboratory of Veterinary Biotechnology of Henan Province, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan, China.. Electronic address: [email protected].
PMID: 41875495 DOI: 10.1016/j.intimp.2026.116545
Abstract

Bovine mastitis is an inflammatory disease, which activates the Apoptosis and Autophagy of bovine mammary epithelial cells (bMECs). HO-1 is a crucial regulatory factor of cellular and tissue homeostatic responses, including anti-apoptotic, anti-inflammatory, and Autophagy regulatory functions. The PI3K/mTOR signaling is a key pathway for regulating cellular Autophagy and Apoptosis. Therefore, we hypothesized that HO-1 relied on PI3K/mTOR signaling to attenuate inflammation by reducing Autophagy and Apoptosis in bMECs. We used LPS to treat bMECs to establish an inflammatory cell model, following treatment with HO-1. Changes in cellular inflammation, Apoptosis, and Autophagy levels were measured using RT-PCR, ELISA, Western blotting, transmission electron microscopy, and flow cytometry methods. Furthermore, when PI3K or mTOR inhibitors and HO-1 were administered before treating with LPS, the regulatory effect of HO-1 on Apoptosis and Autophagy activity were evaluated. We found that HO-1 increased the proliferation of bMECs and alleviated the inflammatory response in bMECs, noticeably attenuating the mRNA abundances and content of pro-inflammatory markers (IL-6, IL-8 and TNF-α) elevated by LPS. Furthermore, HO-1 also displayed anti-apoptotic and anti-autophagy roles. More importantly, the protective roles of HO-1 depended on PI3K/mTOR signaling to mediate the Apoptosis and Autophagy. Certainly, these data showed that HO-1 had potent anti-inflammatory properties, activating PI3K/mTOR signaling pathways and inhibiting inflammatory-induced Apoptosis and Autophagy in bMECs. Together, HO-1 can be used as an effective clinical drug specifically for the treatment of bovine mastitis.

Keywords

Apoptosis; Autophagy; Heme oxygenase-1; Inflammation; PI3K/mTOR signaling.

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