Production of intracellular IL-1alpha, IL-1beta, and IL-1Ra isoforms by activated human dermal and synovial fibroblasts: phenotypic differences between human dermal and synovial fibroblasts.
We compared the production of IL-1alpha, IL-1beta, and of IL-1Ra isoforms by cultured human dermal (HDF) and synovial fibroblasts (HSF) in response to IL-1alpha, TNF-alpha, or direct T cell membrane contact. IL-1Ra was constitutively present in the cell lysates of cultured HDF and its synthesis increased in stimulated cells, whereas IL-1Ra was present in low amounts in the supernatants. Secreted IL-1Ra (sIL-1Ra) and intracellular IL-1Ra type 1 (icIL-1Ra1) mRNA levels followed the same pattern. In stimulated HDF, IL-1alpha and IL-1beta were increased intracellularly but remained undetectable in the supernatants. In HSF, IL-1Ra levels increased in both cell lysates and supernatants upon stimulation. IL-1beta was only present in HSF cell lysates after stimulation, whereas IL-1alpha was undetectable. Both sIL-1Ra and icIL-1Ra1 mRNAs were detected in stimulated HSF. icIL-1Ra1 was the predominant intracellular isoform in both cell types. In conclusion, stimulated HDF produce high amounts of intracellular IL-1Ra, IL-1alpha, and IL-1beta. In contrast, HSF synthesized both intracellular and secreted IL-1Ra, whereas IL-1beta was present only in cell lysates. The presence of high amounts of icIL-1Ra1 and intracellular IL-1alpha in HDF suggests that these cytokines may carry out important function inside cells.
Maret
Michel
M
Division of Rheumatology, Department of Internal Medicine, University Hospital and Department of Pathology & Immunology, University School of Medicine, Av Beau-Séjour 26, 1211 Geneva 14, Switzerland.
Chicheportiche
Rachel
R
Dayer
Jean-Michel
JM
Gabay
Cem
C
D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D042541:Intracellular Space / Q000378:metabolism*; D010641:Phenotype; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D013583:Synovial Membrane / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D020033:Protein Isoforms; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha