Adiponectin attenuates lipopolysaccharide-induced acute lung injury through suppression of endothelial cell activation.

Authors

• Jason M Konter
• Jennifer L Parker
• Elizabeth Baez
• Stephanie Z Li
• Barbara Ranscht
• Martin Denzel
• Frederic F Little
• Kazuto Nakamura
• Noriyuki Ouchi
• Alan Fine
• Kenneth Walsh
• Ross S Summer

Publication/Presentation Date

1-15-2012

Abstract

Adiponectin (APN) is an adipose tissue-derived factor with anti-inflammatory and vascular protective properties whose levels paradoxically decrease with increasing body fat. In this study, APN's role in the early development of ALI to LPS was investigated. Intratracheal LPS elicited an exaggerated systemic inflammatory response in APN-deficient (APN(-/-)) mice compared with wild-type (wt) littermates. Increased lung injury and inflammation were observed in APN(-/-) mice as early as 4 h after delivery of LPS. Targeted gene expression profiling performed on immune and endothelial cells isolated from lung digests 4 h after LPS administration showed increased proinflammatory gene expression (e.g., IL-6) only in endothelial cells of APN(-/-) mice when compared with wt mice. Direct effects on lung endothelium were demonstrated by APN's ability to inhibit LPS-induced IL-6 production in primary human endothelial cells in culture. Furthermore, T-cadherin-deficient mice that have significantly reduced lung airspace APN but high serum APN levels had pulmonary inflammatory responses after intratracheal LPS that were similar to those of wt mice. These findings indicate the importance of serum APN in modulating LPS-induced ALI and suggest that conditions leading to hypoadiponectinemia (e.g., obesity) predispose to development of ALI through exaggerated inflammatory response in pulmonary vascular endothelium.

Volume

188

Issue

2

First Page

854

Last Page

863

ISSN

1550-6606

Published In/Presented At

Konter, J. M., Parker, J. L., Baez, E., Li, S. Z., Ranscht, B., Denzel, M., Little, F. F., Nakamura, K., Ouchi, N., Fine, A., Walsh, K., & Summer, R. S. (2012). Adiponectin attenuates lipopolysaccharide-induced acute lung injury through suppression of endothelial cell activation. Journal of immunology (Baltimore, Md. : 1950), 188(2), 854–863. https://doi.org/10.4049/jimmunol.1100426

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

22156343

Department(s)

Administration and Leadership

Document Type

Article