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Am J Physiol Lung Cell Mol Physiol. 2018 Jan 1;314(1):L127-L136. doi: 10.1152/ajplung.00200.2017. Epub 2017 Aug 31.

IL-8 mediates idiopathic pulmonary fibrosis mesenchymal progenitor cell fibrogenicity.

Author information

1
Department of Medicine, University of Minnesota , Minneapolis, Minnesota.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease, but the mechanisms driving progression remain incompletely defined. We previously reported that the IPF lung harbors fibrogenic mesenchymal progenitor cells (MPCs), which serve as a cell of origin for IPF fibroblasts. Proliferating IPF MPCs are located at the periphery of fibroblastic foci in an active cellular front at the interface between the myofibroblast-rich focus core and adjacent normal alveolar structures. Among a large set of genes that distinguish IPF MPCs from their control counterparts, we identified IL-8 as a candidate mediator of IPF MPC fibrogenicity and driver of fibrotic progression. IPF MPCs and their progeny displayed increased steady-state levels of IL-8 and its cognate receptor CXCR1 and secreted more IL-8 than did controls. IL-8 functioned in an autocrine manner promoting IPF MPC self-renewal and the proliferation and motility of IPF MPC progeny. Secreted IL-8 also functioned in a paracrine manner stimulating macrophage migration. Analysis of IPF lung tissue demonstrated codistribution of IPF MPCs with activated macrophages in the active cellular front of the fibroblastic focus. These findings indicate that IPF MPC-derived IL-8 is capable of expanding the mesenchymal cell population and recruiting activated macrophages cells to actively evolving fibrotic lesions.

KEYWORDS:

IL-8; IPF mesenchymal progenitor cell; fibrotic front; macrophage

PMID:
28860143
PMCID:
PMC5866425
DOI:
10.1152/ajplung.00200.2017
[Indexed for MEDLINE]
Free PMC Article

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