TY - JOUR
T1 - Interleukin-1β and tumor necrosis factor-α induce gene expression and production of leukocyte chemotactic factors, colony-stimulating factors, and interleukin-6 in human mesangial cells
AU - Zoja, Carla
AU - Wang, Ji Ming
AU - Bettoni, Stefania
AU - Sironi, Marina
AU - Renzi, Daniela
AU - Chiaffarino, Francesca
AU - Abboud, Hanna E.
AU - Van Damme, Jo
AU - Mantovani, Alberto
AU - Remuzzi, Giuseppe
AU - Rambaldi, Alessandro
PY - 1991/4
Y1 - 1991/4
N2 - The capacity of human cultured mesangial cells to produce soluble factors potentially relevant for mechanisms of inflammation and immunity at the glomerular site was analyzed. The nature of the secreted factors initially was investigated by Northern blot analysis using total cellular RNAs isolated from resting and activated mesangial cells. On exposure of mesangial cells to human recombinant interleukin-1 β (IL-1β), high levels of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) mRNAs were detected. Similar transcripts were found after stimulation with human recombinant tumor necrosis factor-α (TNF-α). Active secretion of IL-8 was documented by radioimmunoassay in supernatants of mesangial cells activated by either IL-1β, or TNF-α. Using an in vitro migration assay, supernatants from resting mesangial cells were found to be devoid of any chemotactic activity for granulocytes or monotytes. On stimulation with IL-1β, however, mesangial cell supernatants expressed MCP-1 biologic activity detected as induction of a strong migratory response for human monocytes but not for granulocytes. In addition, IL-1β, and TNF-α induced high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) mRNAs. Similarly IL-1β and TNF-α induced the interleukin-6 (IL-6) gene and active secretion of its mature protein. These data strongly support an effector role for mesangial cells in modulating immune-inflammatory responses in glomeruli. Release of cytokines may activate not only infiltrating inflammatory cells through short paracrine pathways, but also mesangial cells themselves through an autocrine pathway.
AB - The capacity of human cultured mesangial cells to produce soluble factors potentially relevant for mechanisms of inflammation and immunity at the glomerular site was analyzed. The nature of the secreted factors initially was investigated by Northern blot analysis using total cellular RNAs isolated from resting and activated mesangial cells. On exposure of mesangial cells to human recombinant interleukin-1 β (IL-1β), high levels of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) mRNAs were detected. Similar transcripts were found after stimulation with human recombinant tumor necrosis factor-α (TNF-α). Active secretion of IL-8 was documented by radioimmunoassay in supernatants of mesangial cells activated by either IL-1β, or TNF-α. Using an in vitro migration assay, supernatants from resting mesangial cells were found to be devoid of any chemotactic activity for granulocytes or monotytes. On stimulation with IL-1β, however, mesangial cell supernatants expressed MCP-1 biologic activity detected as induction of a strong migratory response for human monocytes but not for granulocytes. In addition, IL-1β, and TNF-α induced high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) mRNAs. Similarly IL-1β and TNF-α induced the interleukin-6 (IL-6) gene and active secretion of its mature protein. These data strongly support an effector role for mesangial cells in modulating immune-inflammatory responses in glomeruli. Release of cytokines may activate not only infiltrating inflammatory cells through short paracrine pathways, but also mesangial cells themselves through an autocrine pathway.
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M3 - Article
C2 - 2012180
AN - SCOPUS:0025730125
VL - 138
SP - 991
EP - 1003
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 4
ER -