IL-2 production by myofibroblasts from post-radiation fibrosis in breast cancer patients.
The origin of cell activation in post-radiation fibrosis and its chronic extension are still poorly understood. Since local IL-2 cancer treatment sometimes triggers intraperitoneal fibrosis we have analyzed three myofibroblastic cell strains from post-radiation skin fibrosis (FPR7, FPR10 and FPR15) for their interactions with IL-2. In these cells we have observed the surface expression of the two chains of the IL-2R (IL-2R alpha beta), the presence of the 0.9 kb transcript specific for the IL-2 gene and, by flow cytometry with anti-IL-2 mAbs, the presence of IL-2 immunoreactive material inside the cells up to 8 days after subculture. The FPR cell lines secreted IL-2, as determined by ELISA. The secreted IL-2 is biologically active since it sustains the proliferation of the IL-2-dependent murine lymphoid cell line CTLL2 and preincubation with anti-IL-2 blocking mAbs completely abolishes this activity. Overnight incubation of FPR cells with polyclonal anti-IL-2 antibodies leads to a decreased expression of the membrane adhesion molecules ICAM-1 and CD44, suggesting the existence of an autocrine/paracrine loop involved in the surface expression of these antigens. By contrast, in normal adult skin fibroblasts we did not detect IL-2 gene activation. In vivo, IL-2 secretion by post-radiation fibrosis fibroblasts and the subsequent up-regulation of ICAM-1 and CD44 may represent key events during the process that leads to radiation fibrosis.
Alileche
A
A
U268 INSERM, Hôpital Paul Brousse, Villejuif, France.
Han
D
D
Plaisance
S
S
Assier
E
E
Sahraoui
Y
Y
Clemanceau
C
C
Metivier
D
D
Brouty-Boyer
D
D
Jasmin
C
C
Azzarone
B
B
D001943:Breast Neoplasms / Q000532:radiotherapy*; D002352:Carrier Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology / Q000528:radiation effects*; D005355:Fibrosis / Q000209:etiology / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis*; D011832:Radiation Injuries / Q000276:immunology* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D012867:Skin / Q000276:immunology / Q000473:pathology / Q000528:radiation effects*
D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; D016201:Receptors, Lymphocyte Homing; D018799:Intercellular Adhesion Molecule-1