Human recombinant interleukin-4 induces proliferation and interleukin-6 production by cultured human skin fibroblasts.
The effect of human recombinant interleukin-4 (hrIL-4) on normal human adult dermal fibroblasts in terms of proliferation and IL-6 production was studied. Fibroblasts were exposed to different concentrations of IL-4 for various periods of time. Proliferation was measured using a [3H]thymidine incorporation assay. IL-6 production was measured at the transcriptional, protein, and functional levels by Northern blot analysis, radioimmunoassay, and B9 bioassay, respectively. Our results show that hrIL-4 significantly stimulated (two- to fivefold) fibroblasts to increase the incorporation of [3H]thymidine in a dose- and time-dependent manner. However, hrIL-1, hrIL-2, hrIL-5, or hrTNF alpha, at the same concentration (100 U/ml) and for the same time period (4 days), did not. In addition, IL-4 significantly induced (four- to eightfold) the production of immunoreactive and biologically functional IL-6. However, IL-4 was not as potent an inducer of IL-6 as IL-1. The IL-4-induced IL-6 production was dose and time dependent and was due, at least in part, to a dramatic increase in the steady-state levels of IL-6 mRNA. This is the first report describing the ability of IL-4 to activate human dermal fibroblasts in terms of proliferation and IL-6 production.
Feghali
C A
CA
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Bost
K L
KL
Boulware
D W
DW
Levy
L S
LS
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D011994:Recombinant Proteins / Q000494:pharmacology
D015850:Interleukin-6; D011994:Recombinant Proteins; D015847:Interleukin-4