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
  • 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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