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LPS-induced SOCS3 antagonizes the JAK2-STAT5 pathway and inhibits ß-casein synthesis in bovine mammary epithelial cells.
Geng, Zijian; Shan, Xufei; Lian, Shuai; Wang, Jianfa; Wu, Rui.
Afiliação
  • Geng Z; College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 2 Xinyang Road, Sartu District, Daqing 163319, PR China.
  • Shan X; College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 2 Xinyang Road, Sartu District, Daqing 163319, PR China.
  • Lian S; College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 2 Xinyang Road, Sartu District, Daqing 163319, PR China.; Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, No. 2 Xinyang Road, Sartu District, Daqing 163319, PR China
  • Wang J; College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 2 Xinyang Road, Sartu District, Daqing 163319, PR China.; Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, No. 2 Xinyang Road, Sartu District, Daqing 163319, PR China
  • Wu R; College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 2 Xinyang Road, Sartu District, Daqing 163319, PR China.; Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, No. 2 Xinyang Road, Sartu District, Daqing 163319, PR China
Life Sci ; 278: 119547, 2021 Aug 01.
Article em En | MEDLINE | ID: mdl-33930363
ABSTRACT
Bovine mammary epithelial cells (BMECs) are essential for lactation in the dairy cow mammary gland, and are often used as a cellular model to study changes in inflammatory responses and lactation functions with exogenous stimuli. Prolactin (PRL) promotes milk protein synthesis by continuously activating the Janus kinase 2 and signal transducer and activator of transcription 5 (JAK2-STAT5) pathway. Lipopolysaccharides (LPS) activates inflammatory responses in cells and inhibits casein synthesis, but the exact mechanism is still unclear. Suppressor of cytokine signaling-3 (SOCS3) is a negative regulator of the JAK-STATs signaling pathway, and regulates a variety of inflammatory responses by inhibiting STAT3. Previous studies also suggested that SOCS3 plays a role in the development and involution of bovine mammary glands. The purpose of this study was to investigate whether LPS activated SOCS3, and whether SOCS3 resisted the regulation of casein synthesis by PRL in a JAK2-STAT5-dependent manner. We treated in vitro BMECs with 125 ng/mL PRL, 10 µg/mL LPS, SOCS3 siRNA (silencing), a SOCS3-GFP adenovirus overexpression vector, or combinations, to determine ß-casein expression. We demonstrated that PRL up-regulated phospho-JAK2, phsopho-STAT5 and ß-casein expression, whereas LPS caused the opposite effects, and activated SOCS3. SOCS3 overexpression interrupted the JAK2-STAT5 pathway in BMECs. With SOCS3 was silenced, LPS could not activate the JAK2-STAT5 pathway, and no inhibition of ß-casein expression was observed. In conclusion, we showed that LPS activated SOCS3 in BMECs, antagonized the JAK2-STAT5 pathway via SOCS3 regulation, and ultimately reduced ß-casein expression in these cells.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Caseínas / Lipopolissacarídeos / Fator de Transcrição STAT5 / Janus Quinase 2 / Proteína 3 Supressora da Sinalização de Citocinas / Inflamação Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Caseínas / Lipopolissacarídeos / Fator de Transcrição STAT5 / Janus Quinase 2 / Proteína 3 Supressora da Sinalização de Citocinas / Inflamação Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article