ERK1/2-CEBPB Axis-Regulated hBD1 Enhances Anti-Tuberculosis Capacity in Alveolar Type II Epithelial Cells.
Yaoxin ChenZhenyu HanSian ZhangHonglin LiuKe WangJieyu LiuFeichang LiuShiyun YuNa SaiHaiyan MaiXinying ZhouChaoying ZhouQian WenLi MaPublished in: International journal of molecular sciences (2024)
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 β-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.
Keyphrases
- mycobacterium tuberculosis
- signaling pathway
- pulmonary tuberculosis
- transcription factor
- induced apoptosis
- immune response
- pi k akt
- cell proliferation
- cell cycle arrest
- global health
- poor prognosis
- public health
- dendritic cells
- oxidative stress
- endothelial cells
- epithelial mesenchymal transition
- dna binding
- cell death
- toll like receptor
- pulmonary hypertension
- protein kinase
- metabolic syndrome
- inflammatory response
- human immunodeficiency virus
- binding protein
- mesenchymal stem cells
- long non coding rna
- type diabetes
- drug induced