Neutrophil Elastase and Oxygen Radicals Enhance Monocyte Chemoattractant Protein-1 Expression After Ischemia/Reperfusion in Rat Liver

Yamaguchi, Yasuo; Matsumura, Fujio; Liang, Jian; Okabe, Kazutoshi; Ohshiro, Hajime; Ishihara, Kohjiroh; Matsuda, Takanori; Mori, Katsutaka; Ogawa, Michio

doi:10.1097/00007890-199911270-00005

Cited by 47 publications

(44 citation statements)

References 54 publications

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“…MCP-1 can be upregulated in the liver in vivo by I/R [28] as well as by bacterial endotoxin [29], and in isolated mouse hepatocytes by hypoxia [30] and the present study). The expression of MCP-1 in normoxic, primary cultured hepatocytes was thought to be due to the stress of cell isolation [31], and we likewise found elevated MCP-1 in normoxic hepatocytes.…”

Section: Discussionsupporting

confidence: 72%

Central role for MCP-1/CCL2 in injury-induced inflammation revealed by in vitro, in silico, and clinical studies

Zamora

Ziraldo

Namas

et al. 2013

Journal of Critical Care

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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% O 2 ) or normoxia (21% O 2 ) for 1-72 h, and both the cell supernatants and protein lysates were assayed for 18 inflammatory mediators by Luminex TM 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-1a 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.

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Section: Discussionsupporting

confidence: 72%

Central role for MCP-1/CCL2 in injury-induced inflammation revealed by in vitro, in silico, and clinical studies

Zamora

Ziraldo

Namas

et al. 2013

Journal of Critical Care

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“…Ischemia/reperfusion models, unlike APAP models, have shown that MCP-1 is increased by reactive oxygen species and may produce injury by increasing ICAM-1 expression on hepatic endothelium (194). Reducing this chemokine decreases subsequent injury (193), suggesting that reperfusion-induced inflammation and subsequent oxygen radical production may occur by a mechanism distinct from that of APAP. In chronic alcoholic liver disease and cirrhosis (21), MCP-1 is required for infiltration of monocytes and subsequent inflammation and fibrosis, and expression levels correlate with AST levels and severity of injury (2,50,123).…”

Section: Produced By Dendritic Cells That Attracts T Cells and Naturamentioning

confidence: 99%

Chemokines and chemokine receptors in leukocyte trafficking

Olson

Ley

2002

American Journal of Physiology-Regulatory, Integrative and Comp

579

445

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mokines regulate inflammation, leukocyte trafficking, and immune cell differentiation. The role of chemokines in homing of naive T lymphocytes to secondary lymphatic organs is probably the best understood of these processes, and information on chemokines in inflammation, asthma, and neurological diseases is rapidly increasing. Over the past 15 years, understanding of the size and functional complexity of the chemokine family of peptide chemoattractants has grown substantially. In this review, we first present information regarding the structure, expression, and signaling properties of chemokines and their receptors. The second part is a systems physiology-based overview of the roles that chemokines play in tissue-specific homing of lymphocyte subsets and in trafficking of inflammatory cells. This review draws on recent experimental findings as well as current models proposed by experts in the chemokine field.

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“…Moreover, PMN protease inhibitors protected the liver from injury caused by ischemia-reperfusion, although this attenuation was accompanied by a decrease in circulating chemokines and hepatic PMN accumulation (Yamaguchi et al, 1997). Thus, PMN proteases might contribute to hepatocellular injury by mechanisms independent of direct hepatocyte killing (Yamaguchi et al, 1997(Yamaguchi et al, , 1999Soejima et al, 1999). It is possible that PMN proteases induce intracellular oxidative stress in hepatocytes, which could be exacerbated by glutathione peroxidase deficiency.…”

Section: Neutrophilsmentioning

confidence: 99%

Inflammatory Stress and Idiosyncratic Hepatotoxicity: Hints from Animal Models

et al. 2009

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Neutrophil Elastase and Oxygen Radicals Enhance Monocyte Chemoattractant Protein-1 Expression After Ischemia/Reperfusion in Rat Liver

Abstract: MCP-1 production by macrophages is stimulated by neutrophil elastase and oxygen radicals generated by hypoxia, probably due to microthrombus formation after ischemia/reperfusion of the rat liver.

Cited by 47 publications

References 54 publications

Central role for MCP-1/CCL2 in injury-induced inflammation revealed by in vitro, in silico, and clinical studies

Central role for MCP-1/CCL2 in injury-induced inflammation revealed by in vitro, in silico, and clinical studies

Chemokines and chemokine receptors in leukocyte trafficking

Inflammatory Stress and Idiosyncratic Hepatotoxicity: Hints from Animal Models

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