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ERK1/2-CEBPB Axis-Regulated hBD1 Enhances Anti-Tuberculosis Capacity in Alveolar Type II Epithelial Cells.
Chen, Yaoxin; Han, Zhenyu; Zhang, Sian; Liu, Honglin; Wang, Ke; Liu, Jieyu; Liu, Feichang; Yu, Shiyun; Sai, Na; Mai, Haiyan; Zhou, Xinying; Zhou, Chaoying; Wen, Qian; Ma, Li.
Afiliação
  • Chen Y; Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.
  • Han Z; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangzhou 510515, China.
  • Zhang S; Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.
  • Liu H; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangzhou 510515, China.
  • Wang K; Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.
  • Liu J; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangzhou 510515, China.
  • Liu F; Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.
  • Yu S; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangzhou 510515, China.
  • Sai N; Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.
  • Mai H; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangzhou 510515, China.
  • Zhou X; Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.
  • Zhou C; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangzhou 510515, China.
  • Wen Q; Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.
  • Ma L; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangzhou 510515, China.
Int J Mol Sci ; 25(4)2024 Feb 18.
Article em En | MEDLINE | ID: mdl-38397085
ABSTRACT
Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis with substantial morbidity and mortality rates. Type II alveolar epithelial cells (AEC-II) play a critical role in the pulmonary immune response against Mtb infection by secreting effector molecules such as antimicrobial peptides (AMPs). Here, human ß-defensin 1 (hBD1), an important AMP produced by AEC-II, has been demonstrated to exert potent anti-tuberculosis activity. HBD1 overexpression effectively inhibited Mtb proliferation in AEC-II, while mice lacking hBD1 exhibited susceptibility to Mtb and increased lung tissue inflammation. Mechanistically, in A549 cells infected with Mtb, STAT1 negatively regulated hBD1 transcription, while CEBPB was the primary transcription factor upregulating hBD1 expression. Furthermore, we revealed that the ERK1/2 signaling pathway activated by Mtb infection led to CEBPB phosphorylation and nuclear translocation, which subsequently promoted hBD1 expression. Our findings suggest that the ERK1/2-CEBPB-hBD1 regulatory axis can be a potential therapeutic target for anti-tuberculosis therapy aimed at enhancing the immune response of AEC-II cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose / Beta-Defensinas / Mycobacterium tuberculosis Limite: Animals / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose / Beta-Defensinas / Mycobacterium tuberculosis Limite: Animals / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China