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PMID: 12707030 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Impact of interleukin-13 responsiveness on the synthetic and proliferative properties of Th1- and Th2-type pulmonary granuloma fibroblasts.

The American journal of pathology ·Vol. 162 ·No. 5 ·2003-05-00 ·Pages 1475-86

Jakubzick C, Choi ES, Kunkel SL, Joshi BH, Puri RK, Hogaboam CM

Abstract

Interleukin-13 (IL-13) has emerged as a major cytokine mediator of fibroblast activation and pulmonary fibrosis. Normal (from noninflamed lung), Th1-type (induced by the pulmonary embolization of purified peptide derivative-coated beads in mice sensitized to purified peptide derivative), and Th2-type (induced by the pulmonary embolization of Schistosoma mansoni egg antigen-coated beads in mice sensitized with S. mansoni eggs) primary fibroblast cell lines all exhibited constitutive gene expression of two receptor chains that bind and signal IL-13-mediated cellular events: IL-4Ralpha and IL-13Ralpha1. However, all three fibroblast cell lines exhibited divergent synthetic and proliferative responses to the exogenous addition of either recombinant IL-13 or a chimeric protein comprised of IL-13 and a truncated version of Pseudomonas exotoxin (IL13-PE), which targets and kills IL-13 receptor overexpressing cells. The exogenous addition of IL-13 to Th1-type and Th2-type fibroblast cultures significantly increased the cellular expression of IL-13Ralpha2, which may function as an IL-13 decoy receptor. After a 24-hour exposure to IL-13, the total collagen generation and cellular proliferation by Th2-type fibroblasts were significantly higher than that observed in similar numbers of normal and Th1-type fibroblasts. In addition IL13-PE, which binds with highest affinity to IL-13Ralpha2, exhibited down-regulatory effects on proliferation and matrix generation expression by Th1- and Th2-type, but not normal, fibroblasts. Thus, these data demonstrate that fibroblasts derived from murine pulmonary granulomas exhibit divergent expression of functional IL-13 receptor and this expression dictates the responsiveness and susceptibility to recombinant IL-13 and IL-13 immunotoxin, respectively.

MeSH Terms
Animals Cell Division/drug effects Cells, Cultured Female Fibroblasts/drug effects,immunology,pathology Gene Expression Regulation/drug effects Interleukin-13/pharmacology Interleukin-13 Receptor alpha1 Subunit Lymphocyte Activation/drug effects Mice Mice, Inbred CBA Plasma Cell Granuloma, Pulmonary/immunology,pathology Receptors, Interferon/analysis Receptors, Interleukin/analysis Receptors, Interleukin-13 Th1 Cells/immunology Th2 Cells/immunology
Chemicals
Il13ra1 protein, mouse Interleukin-13 Interleukin-13 Receptor alpha1 Subunit Receptors, Interferon Receptors, Interleukin Receptors, Interleukin-13 interferon gamma receptor
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Jakubzick Claudia
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Choi Esther S
Kunkel Steven L
Joshi Bharat H
Puri Raj K
Hogaboam Cory M
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)64280-0
Published
2003-05-00
Pages
1475-86
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1851205
Subset
IM
Grants
NIAID NIH HHS · T32 AI007413 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)64280-0 PMC Full Text View journal details
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