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Chemokines and Their Receptors in Fibrosis

  • Chapter
The Chemokine Receptors

Part of the book series: The Receptors ((REC))

Abstract

Tissue fibrosis, which results in the destruction of normal organ function, is a leading cause of morbidity and mortality. Current strategies for treating fibrosis have been unsuccessful, largely because of the difficulty in distinguishing whether inflammatory or fibrogenic events sustain the progression of the disease. The causes of fibrosis are diverse regardless of the tissue involved, and the common features include the sequential recruitment of inflammatory cells, overproliferation of matrix-producing cells, and the overproduction of extracellular matrix. An excessive wound-healing response presumably represents disruption in this sequence thereby leading to a disturbance in the balance between tissue remodeling, matrix degradation, and permanent scarring. The mechanisms involved in pulmonary fibrosis also represent three sequential events characterized by an initial insult, inflammation, and tissue repair. Central to the progression of these events is the balance between a T helper 1 (Th1) and a T helper 2 (Th2) environment, in which Th2-specific signals have been shown to be immunomodulatory and profibrotic. However, the release of these Th2-specific cytokines and chemokines by both inflammatory and resident cells maintains the fibrotic response, consequently leading to fibrotic disease. Evidence from animal models and human studies have identified a number of Th1/Th2-associated chemokines and chemokine receptors as profibrotic or antifibrotic. Therefore, investigating the chemokines, chemokine receptors, and the cells that they impact is an attractive approach to identifying therapeutic targets in fibrosis.

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Authors and Affiliations

  1. Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA

    Glenda Trujillo & Cory M. Hogaboam

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  1. Glenda Trujillo
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  1. Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL

    Jeffrey K. Harrison PhD

  2. Department of Pathology and Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI

    Nicholas W. Lukacs PhD

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Trujillo, G., Hogaboam, C.M. (2007). Chemokines and Their Receptors in Fibrosis. In: Harrison, J.K., Lukacs, N.W. (eds) The Chemokine Receptors. The Receptors. Humana Press. https://doi.org/10.1007/978-1-59745-020-1_14

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