Human pulmonary fibroblasts exhibit altered interleukin-4 and interleukin-13 receptor subunit expression in idiopathic interstitial pneumonia.
Abnormal proliferation of pulmonary fibroblasts is a prominent feature of chronic pulmonary fibrotic diseases such as idiopathic interstitial pneumonia (IIP), but it is not presently clear how this proliferative response by lung fibroblasts can be therapeutically modulated. In the present study, we examined whether it was possible to selectively target primary human pulmonary fibroblasts grown out of surgical lung biopsies (SLBs) from IIP patients based on their expression of interleukin-4 receptor (IL-4R) and IL-13R subunits. Pulmonary fibroblast lines cultured from patients with the severest form of IIP, namely usual interstitial pneumonia, exhibited the greatest gene and protein expression of IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2 compared with primary pulmonary fibroblast lines grown from other IIP SLBs and normal SLBs. When exposed to increasing concentrations of a chimeric protein comprised of human IL-13 and a truncated version of Pseudomonas exotoxin (IL13-PE), the proliferation of primary usual interstitial pneumonia fibroblasts was inhibited to a much greater extent compared with fibroblast lines from nonspecific interstitial pneumonia and respiratory bronchiolitis/interstitial lung disease patient groups. Fibroblasts from normal patients exhibited minimal susceptibility to the cytotoxic effect of IL13-PE. IL13-PE-mediated targeting of IIP fibroblasts was dependent on their expression of IL-4Ralpha and IL-13Ralpha2. Thus, these data suggest that the abnormal proliferative properties of human lung fibroblasts from certain IIP patient groups can be modulated in a manner that is dependent on the IL-4 and IL-13 receptor subunit expression by these cells.
Jakubzick
Claudia
C
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602, USA.
Choi
Esther S
ES
Carpenter
Kristin J
KJ
Kunkel
Steven L
SL
Evanoff
Holly
H
Martinez
Fernando J
FJ
Flaherty
Kevin R
KR
Toews
Galen B
GB
Colby
Thomas V
TV
Travis
William D
WD
Joshi
Bharat H
BH
Puri
Raj K
RK
Hogaboam
Cory M
CM
D001483:Base Sequence; D001706:Biopsy; D002455:Cell Division; D002478:Cells, Cultured; D017931:DNA Primers; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D053661:Interleukin-13 Receptor alpha1 Subunit; D017563:Lung Diseases, Interstitial / Q000276:immunology* / Q000473:pathology*; D021122:Protein Subunits / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics*; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; C508181:IL13RA1 protein, human; D053661:Interleukin-13 Receptor alpha1 Subunit; D021122:Protein Subunits; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4