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Chemokines as Mediators of Toxicant-Induced Inflammation and Fibrosis

Molecular and Cellular Aspects of Toxicology

  1. François Huaux,
  2. Sandra Lo Re MSc,
  3. Dominique Lison MD, PhD

Published Online: 15 DEC 2009

DOI: 10.1002/9780470744307.gat160

General, Applied and Systems Toxicology

General, Applied and Systems Toxicology

How to Cite

Huaux, F., Lo Re, S. and Lison, D. 2009. Chemokines as Mediators of Toxicant-Induced Inflammation and Fibrosis. General, Applied and Systems Toxicology. .

Author Information

  1. Université catholique de Louvain, Louvain Centre for Toxicology and Applied Pharmacology, Faculty of Medicine, Brussels, Belgium

Publication History

  1. Published Online: 15 DEC 2009

Abstract

There is compelling evidence that chemokines are implicated in the development of tissue inflammation and fibrosis induced by xenobiotics. This chapter reviews recent experimental observations which further delineate how chemokines and their receptors participate in the development of these adverse reactions. Studies tracking chemokines and chemokine receptors show their marked expression in murine lung or liver tissue after exposure to very diverse toxicants inducing inflammation and fibrosis, such as certain inorganic particles (silica), antibiotics (bleomycin) and industrial solvents (carbon tetrachloride, CCl4). Chemokines control leukocyte trafficking in response to these toxic agents. This is supported by evidence that antibody or genetic blockade of the CCL2/CCR2, CXCL1–2/CXCR1–2 as well as CCL11/CCR3 chemokine/receptor pairs reduce toxicant-induced inflammation or fibrosis by limiting the pathological migration of macrophages, neutrophils or eosinophils, respectively. However, the control of chemokine expression is not always associated with the impairment of leukocyte infiltration, and animal models of lung and liver toxicity have highlighted unexpected functions for chemokines including the orchestration of cellular differentiation and angiogenesis as well as fibrocyte tissue accumulation. Although these recent experimental studies do not yet provide a completely clear insight into the exact role of chemokines in the pathogenesis of these diseases in humans, the recognition that chemokines and their receptors are able to determine the persistence of inflammatory cell infiltrates and fibroproliferative repair in response to toxicants has opened a new area of research. Future studies will be directed at the potential implications of novel chemokine-based therapies for the unsolved inflammatory and fibrotic responses associated with toxic agent exposure.

Keywords:

  • chemokines;
  • leukocyte trafficking;
  • cytokines;
  • inflammation;
  • fibrosis;
  • liver;
  • lung;
  • silica;
  • bleomycin;
  • carbon tetrachloride