Back to Search
Start Over
Involvement of multiple transcription factors in regulation of IL-β-induced MCP-1 expression in alveolar type II epithelial cells.
- Source :
-
Molecular Immunology . Jul2019, Vol. 111, p95-105. 11p. - Publication Year :
- 2019
-
Abstract
- • IL-1β stimulates MCP-1 production in alveolar type II epithelial cells. • IKK/NF-κB p65, JNK/c-Jun, and C/EBPβ/δ signaling pathways are activated by IL-1β. • IKK/NF-κB p65/κB element, JNK/c-Jun/AP-1 site, C/EBPβ/δ/C/EBP binding site, and Sp1/Sp1 element contribute to MCP-1 transcription. During acute lung injury, a large number of monocytes are recruited into the pulmonary tissue, which is mainly mediated by local production of monocyte chemotactic protein 1 (MCP-1). As an essential component of the lung tissues, alveolar type II epithelial cells are one of the major sources of MCP-1. Therefore, uncovering the mechanism whereby MCP-1 production is regulated in the alveolar type II cells will provide a pivotal theoretical basis for clinical intervention in acute lung injury. In the current study, we find that there is a κB binding site in the MCP-1 promoter region, and mutation of the site leads to reduced production of MCP-1 in alveolar type II epithelial cells. In contrast, overexpression of NF-κB p65 significantly increases MCP-1 expression. Furthermore, we elucidate that IKKα/β—NF-κB p65 signaling pathway and phosphorylation of serine 534 in NF-κB p65 are required for the maximal expression of MCP-1. Also, Activator protein 1 (AP-1) site in the promoter region and JNK1/2—c-Jun signaling are required for MCP-1 generation in alveolar type II epithelial cells. Moreover, a CCAAT/enhancer-binding protein (C/EBP) element is identified in the MCP-1 promoter region through the point mutation technique, and further experiments demonstrate that both C/EBPβ and C/EBPδ are involved in basic and IL-1β-mediated MCP-1 expression. Of note, specificity protein 1—Sp1 expression is not changed in alveolar type II epithelial cells incubated with IL-1β, but it still control MCP-1 production by binding to the consensus sequence in the promoter region. More importantly, we find that the results derived from the cell line—MLE-12 cells and primary cells are consistent. Taken together, our data provide insights into the molecular mechanism how MCP-1 expression in inflammatory alveolar type II epithelial cells is regulated at transcription level. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01615890
- Volume :
- 111
- Database :
- Academic Search Index
- Journal :
- Molecular Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 136825299
- Full Text :
- https://doi.org/10.1016/j.molimm.2019.04.013