MyD88 deficiency in mammary epithelial cells attenuates lipopolysaccharide (LPS)-induced mastitis in mice.

Autor: Lin X; State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; College of Animal Science and Technology, China Agricultural University, Beijing 100193, China., Zhao Z; State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; College of Animal Science and Technology, China Agricultural University, Beijing 100193, China., Cai Y; State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; College of Animal Science and Technology, China Agricultural University, Beijing 100193, China., He Y; State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; College of Animal Science and Technology, China Agricultural University, Beijing 100193, China., Wang J; State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; College of Animal Science and Technology, China Agricultural University, Beijing 100193, China., Liu N; State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing 100193, China., Qin Y; State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing 100193, China. Electronic address: qinyinghe@cau.edu.cn., Wu Y; State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China; College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing 100193, China. Electronic address: wuyingjie@cau.edu.cn.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Dec 20; Vol. 739, pp. 150569. Date of Electronic Publication: 2024 Aug 19.
DOI: 10.1016/j.bbrc.2024.150569
Abstrakt: Lactation mastitis is a debilitating inflammatory mammary disease in postpartum animals. Myeloid differentiation primary response protein MyD88 is the key downstream adapter for innate pattern recognition receptor toll-like receptor 4 (TLR4), which plays an important role in inflammation. However, the specific role of MyD88 in mammary epithelial cells in the progression of mastitis has not been investigated. In this study, lipopolysaccharide (LPS)-induced mouse mastitis model was used and cytokines such as Tnf-α, Il-1β, Il-6, Cxcl1, Cxcl2 and Ccl2 were significantly increased in inflammatory mammary gland as shown by real time-qPCR. However, the mice with MyD88-deficienet in mammary epithelial cells (cKO) showed a reduction in the expression of Tnf-α, Il-1β, Il-6, Cxcl1 and Cxcl2 in mammary gland compared with control mice, when subjected to LPS induced mastitis. Immunohistochemical staining of cleaved caspase-3 showed that the cell apoptosis induced by inflammation were decreased in MyD88 cKO mice. Furthermore, there were significantly fewer infiltrating inflammatory cells in alveolar lumen of MyD88 cKO mice, including Ly6G-positive neutrophils and F4/80-positive macrophages. RNA-seq in LPS treated mammary glands showed that MyD88 cKO mice had significantly downregulated inflammation-related genes and upregulated genes related to anti-inflammation processes and lipid metabolism compared with control mice. Thus, these results demonstrate that MyD88 in mammary epithelial cells is essential for mastitis progression. And this study not only has important implications for understanding the innate immune response in mammary epithelial cells, but also potentially helps the development of new therapeutic drugs for treating mastitis.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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