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United States Department of Agriculture

Agricultural Research Service

Research Project: BONE METABOLISM IN OBESITY Title: Critical role for CCAAT/Enhancer-binding protein beta in immune complex-induced acute lung injury

Authors
item Yan, Chuanguang -
item Wu, Min -
item Cao, Jay
item Tang, Huifang -
item Johnson, Peter -
item Gao, Hongwei -

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 21, 2012
Publication Date: August 1, 2012
Repository URL: http://handle.nal.usda.gov/10113/56831
Citation: Yan, C., Wu, M., Cao, J.J., Tang, H., Zhu, M., Johnson, P.E., Gao, H. 2012. Critical role for CCAAT/Enhancer-binding protein beta in immune complex-induced acute lung injury. Journal of Immunology. 189(3):1480-90.

Interpretive Summary: This study investigated the molecular mechanisms of inflammation in the pathogenesis of acute lung injury (ALI) and role of the CCAAT/enhancer-binding protein (C/EBP)', -' and -' in the regulation of inflammatory. Using two models of acute lung injury, we demonstrate that C/EBPß, -d, and -' play important regulatory roles in lung inflammatory responses. We show that C/EBP' deficiency significantly reduced IgG immune complex-stimulated inflammatory responses in alveolar macrophages and injured lung, whereas C/EBP' is critical for LPS-induced acute lung injury. Moreover, overexpression of C/EBP' in lung using a recombinant adenovirus encoding murine C/EBP' resulted in substantial decreases of lung inflammatory injury induced by both IgG immune complex and LPS. Our findings identify the C/EBP transcription factors are critical mediators of both the pro- and anti-inflammatory mechanisms in acute lung injury.

Technical Abstract: Although inflammation plays a central role in the pathogenesis of acute lung injury (ALI), the molecular mechanisms underlying inflammatory responses in ALI are poorly understood, and therapeutic options remain limited. The CCAAT/enhancer-binding protein (C/EBP) gamma and -gamma have been implicated in the regulation of inflammatory mediators, while the role of C/EBP in inflammation remains elusive. C/EBP beta, -delta, and -gamma are all expressed in the lung; however, their function in lung are not clear. Here, using two models of acute lung injury, we demonstrate that C/EBP beta, -delta, and -gamma play important regulatory roles in lung inflammatory responses. We show that C/EBP gamma deficiency significantly reduced IgG immune complex-stimulated inflammatory responses in alveolar macrophages and injured lung, whereas C/EBP gamma is critical for LPS-induced acute lung injury. Moreover, overexpression of C/EBP gamma in lung using a recombinant adenovirus encoding murine C/EBP gamma resulted in substantial decreases of lung inflammatory injury induced by both IgG immune complex and LPS. These findings identify the same family of C/EBP transcription factors as critical mediators of both the pro- and anti-inflammatory mechanisms in acute lung injury.

Last Modified: 8/27/2014
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