International Immunology, Vol 10, 1103-1110, Copyright © 1998 by Oxford University Press
T Murata, SR Husain, H Mohri and RK Puri
IL-13 and IL-4, pleiotropic immune regulatory cytokines, have been shown to
mediate similar prominent effects in human fibroblast cell lines. However,
molecular mechanisms for their redundant effects are not known. Here, we
have investigated the structure of IL-13 receptors (IL-13R) and molecular
mechanisms of signal transduction through IL-13 and IL-4 receptors in
non-transformed normal skin fibroblast cell lines. We demonstrate that
high-affinity IL-13R is expressed in normal skin fibroblast cell lines.
Upon [125I]1L-13 cross-linking, a approximately 60-70 kDa band was observed
in sk559 and sk574 fibroblast cell lines. By RT-PCR analysis, mRNA for
IL-13R alpha, IL-13R alpha' and IL-4Rbeta chains were expressed; however,
the IL-2Rgamma chain, shown to participate and modulate IL-4 and IL-13
binding, was not expressed in any of the cell lines examined. The Janus
kinase (JAK)2 and Tyk2 were phosphorylated in response to IL-4 or IL-13 in
sk559 and sk574 cell lines. JAK1 was also phosphorylated in one of two cell
lines while JAK3 was present but not phosphorylated in any of the cell
lines studied. A signal transduction and activator of transcription (STAT)6
was also activated in response to both IL. An insulin receptor substrate
(IRS)-1 was constitutively phosphorylated and its phosphorylation level was
augmented in response to both IL. These results suggest that the mechanism
of signal transduction through IL-13 and IL-4 receptors in human fibroblast
cell lines is similar, and this may, at least in part, be responsible for
the redundant effects of these two cytokines. In addition, JAK2 tyrosine
kinase instead of JAK3 appears to play a major role in IL-4- and
IL-13-induced signal transduction in human fibroblasts.
ARTICLES
Two different IL-13 receptor chains are expressed in normal human skin fibroblasts, and IL-4 and IL-13 mediate signal transduction through a common pathway
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
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