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The elicitation of neutrophils and monocytes from the circulation into the inflamed glomerulus is a key process in the pathogenesis of proliferative glomerulonephritis. The aim of this study was to determine the factors which regulate the expression and synthesis of the monocyte specific chemotaxin, monocyte chemotactic peptide 1 (MCP-1). Mesangial cells in culture did not constitutively express MCP-1, but could be induced to express both MCP-1 mRNA and antigenic MCP-1 by either stimulation with IL-1 alpha or TNF alpha, which are also stimuli for interleukin 8 (IL-8/NAP-1) expression and release. Pre-treatment of mesangial cells with the IL-1 receptor antagonist (IL-1ra) induced dose-dependent inhibition of both the expression of MCP-1 and IL-8 mRNA as well as the release of both chemotactic peptides in response to IL-1 alpha, while the receptor antagonist had no significant effect on TNF alpha induced MCP-1 and IL-8 generation. This study demonstrates that the IL-1 receptor antagonist was four times more effective at inhibiting the IL-1 induced expression and release of IL-8 compared to that of MCP-1. These results suggest that mesangial cell-derived MCP-1 may play an important role in the recruitment of monocytes in glomerular inflammation and that an IL-1 receptor antagonist may have therapeutic potential for the treatment of glomerulonephritis.
Z Brown, and
R M Strieter, and
G H Neild, and
R C Thompson, and
S L Kunkel, and
J Westwick
March 1993,
Clinical and experimental immunology,
Z Brown, and
R M Strieter, and
G H Neild, and
R C Thompson, and
S L Kunkel, and
J Westwick
January 1998,
Nephron,
Z Brown, and
R M Strieter, and
G H Neild, and
R C Thompson, and
S L Kunkel, and
J Westwick
February 1994,
The Journal of laboratory and clinical medicine,
Z Brown, and
R M Strieter, and
G H Neild, and
R C Thompson, and
S L Kunkel, and
J Westwick
December 1993,
Journal of immunology (Baltimore, Md. : 1950),
Z Brown, and
R M Strieter, and
G H Neild, and
R C Thompson, and
S L Kunkel, and
J Westwick
December 2000,
Nephron,
Z Brown, and
R M Strieter, and
G H Neild, and
R C Thompson, and
S L Kunkel, and
J Westwick
April 2012,
American journal of physiology. Lung cellular and molecular physiology,
Z Brown, and
R M Strieter, and
G H Neild, and
R C Thompson, and
S L Kunkel, and
J Westwick
October 2005,
American journal of physiology. Heart and circulatory physiology,
Z Brown, and
R M Strieter, and
G H Neild, and
R C Thompson, and
S L Kunkel, and
J Westwick
April 2016,
The Annals of otology, rhinology, and laryngology,
Z Brown, and
R M Strieter, and
G H Neild, and
R C Thompson, and
S L Kunkel, and
J Westwick
October 2000,
Biochemical and biophysical research communications,
Z Brown, and
R M Strieter, and
G H Neild, and
R C Thompson, and
S L Kunkel, and
J Westwick
September 1997,
Kidney international. Supplement,
