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

Carla Zoja, Ji Ming Wang, Stefania Bettoni, Marina Sironi, Daniela Renzi, Francesca Chiaffarino, Hanna E. Abboud, Jo Van Damme, Alberto Mantovani, Giuseppe Remuzzi, Alessandro Rambaldi

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)991-1003
Number of pages13
JournalAmerican Journal of Pathology
Volume138
Issue number4
Publication statusPublished - Apr 1991

Fingerprint

Colony-Stimulating Factors
Mesangial Cells
Chemotactic Factors
Interleukin-1
Interleukin-6
Leukocytes
Tumor Necrosis Factor-alpha
Gene Expression
Macrophage Colony-Stimulating Factor
Chemokine CCL2
Interleukin-8
Granulocytes
Messenger RNA
Granulocyte-Macrophage Colony-Stimulating Factor
Northern Blotting
Radioimmunoassay
Monocytes
Cultured Cells
Immunity
RNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

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. / Zoja, Carla; Wang, Ji Ming; Bettoni, Stefania; Sironi, Marina; Renzi, Daniela; Chiaffarino, Francesca; Abboud, Hanna E.; Van Damme, Jo; Mantovani, Alberto; Remuzzi, Giuseppe; Rambaldi, Alessandro.

In: American Journal of Pathology, Vol. 138, No. 4, 04.1991, p. 991-1003.

Research output: Contribution to journalArticle

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abstract = "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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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

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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

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