RT info:eu-repo/semantics/article
T1 Central Role for MCP-1/CCL2 in Injury-Induced Inflammation Revealed by In Vitro, In Silico, and Clinical Studies
A1 Ziraldo, Cordelia
A1 Vodovotz, Yoram
A1 Namas, Rami A.
A1 Almahmoud, Khalid
A1 Tapias, Victor
A1 Mi, Qi
A1 Barclay, Derek
A1 Jefferson, Bahiyyah S.
A1 Chen, Guoqiang
A1 Billiar, Timothy R.
A1 Zamora, Ruben
AB The translation of in vitro findings to clinical outcomes is often elusive. Trauma/hemorrhagic shock (T/HS) results in hepatic hypoxia that drives inflammation. We hypothesize that in silico methods would help bridge in vitro hepatocyte data and clinical T/HS, in which the liver is a primary site of inflammation. Primary mouse hepatocytes were cultured under hypoxia (1% O2) or normoxia (21% O2) for 1-72 h, and both the cell supernatants and protein lysates were assayed for 18 inflammatory mediators by Luminex™ technology. Statistical analysis and data-driven modeling were employed to characterize the main components of the cellular response. Statistical analyses, hierarchical and k-means clustering, Principal Component Analysis, and Dynamic Network Analysis suggested MCP-1/CCL2 and IL-1α as central coordinators of hepatocyte-mediated inflammation in C57BL/6 mouse hepatocytes. Hepatocytes from MCP-1-null mice had altered dynamic inflammatory networks. Circulating MCP-1 levels segregated human T/HS survivors from non-survivors. Furthermore, T/HS survivors with elevated early levels of plasma MCP-1 post-injury had longer total lengths of stay, longer intensive care unit lengths of stay, and prolonged requirement for mechanical ventilation vs. those with low plasma MCP-1. This study identifies MCP-1 as a main driver of the response of hepatocytes in vitro and as a biomarker for clinical outcomes in T/HS, and suggests an experimental and computational framework for discovery of novel clinical biomarkers in inflammatory diseases.
SN 1932-6203
YR 2013
FD 2013
LK https://uvadoc.uva.es/handle/10324/63880
UL https://uvadoc.uva.es/handle/10324/63880
LA eng
NO PLoS ONE, Diciembre 2013, vol. 8, n. 12, p. e79804
NO Producción Científica
DS UVaDOC
RD 26-may-2024