Soluble Immune Complexes Stimulate Production of Interleukin-1 by Cultured Rat Glomerular Mesangial Cells

1991 ◽  
Vol 11 (2) ◽  
pp. 138-143 ◽  
Author(s):  
Koichi Matsumoto ◽  
Michinobu Hatano
Keyword(s):  
Immune Complexes ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Glomerular Mesangial Cells ◽  
Soluble Immune Complexes

Regulation of mesangial cell cyclooxygenase synthesis by cytokines and glucocorticoids

1992 ◽  
Vol 263 (1) ◽  
pp. F97-F102 ◽  
Author(s):  
D. W. Coyne ◽  
M. Nickols ◽  
W. Bertrand ◽  
A. R. Morrison
Keyword(s):  
Time Course ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Cell Types ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Prostaglandin Production ◽  
Arachidonate Release ◽  
Necrosis Factor

The cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), potently induce prostaglandin formation in glomerular mesangial cells. Mechanisms by which these cytokines stimulate prostaglandin formation vary among cell types. We investigated whether alterations in phospholipase A2 (PLA2) or cyclooxygenase (COX) mass and activity contribute to the changes in mesangial cell prostaglandin production. These cytokines induced COX activity and mass in a time-dependent manner, which paralleled prostaglandin production. IL-1 increased COX mass approximately threefold by 24 h. TNF had a much smaller effect, although it appeared to be additive with IL-1. IL-1-induced COX mass was maintained at an increased level for at least 48 h. The glucocorticoid dexamethasone (DEX) virtually abolished prostaglandin production and blocked cytokine induction of COX activity and mass. DEX did not reduce COX activity or mass below the basal, serum-fed levels, however. By utilizing stable isotope methods, we could demonstrate that IL-1 increased free arachidonate levels, implying new PLA2 synthesis over a time course that was maximal at 6 h and was cycloheximide and actinomycin D sensitive. These data demonstrate that the cytokines IL-1 and TNF enhance synthesis of COX and PLA2, contributing to increased prostaglandin production. Cytokine-stimulated prostaglandin production ceases when cells are also treated with DEX, although control levels of COX activity and mass remain. This occurs because DEX inhibits the IL-1-induced enhanced arachidonate release.

scholarly journals Molecular characterization of a low-molecular-mass matrix metalloproteinase secreted by glomerular mesangial cells as PUMP-1

1992 ◽  
Vol 285 (3) ◽  
pp. 899-905 ◽  
Author(s):  
H P Marti ◽  
L McNeil ◽  
G Thomas ◽  
M Davies ◽  
D H Lovett
Keyword(s):  
Mesangial Cells ◽  
Polyclonal Antibodies ◽  
Mass Matrix ◽  
Interleukin 1 ◽  
Acute Glomerulonephritis ◽  
Glomerular Mesangial Cells ◽  
Tissue Specific ◽  
Specific Manner ◽  
Necrosis Factor

A polymerase chain reaction (PCR)-based homology cloning strategy was used to define the spectrum of stromelysin-like matrix metalloproteinases (MMPs) synthesized by cultured glomerular mesangial cells (MC). Using this technique, cDNAs encoding an unusual, truncated member of the MMP family, punctuated (putative) metalloproteinase (PUMP-1), were exclusively isolated. Incubation with the cytokines interleukin 1 and tumour necrosis factor increased the abundance of PUMP-1 mRNA in mesangial cells. The mesangial PUMP-1 mRNA is processed in a tissue-specific manner, yielding a transcript containing repeated 3′-untranslated region ATTTA motifs commonly found in cytokines with limited mRNA stability. Polyclonal antibodies prepared against the C-terminal region of the PUMP-1 protein documented release of this enzyme by cultures of cytokine-stimulated MC and permitted identification of PUMP-1-expressing mesangial cells within clinical biopsy specimens of acute glomerulonephritis. These findings represent new molecular and clinical evidence that non-malignant cells process and secrete this unusual member of the MMP family in a cytokine-mediated, tissue-specific manner. Mesangial synthesis of PUMP-1 may contribute to the progression of injury during glomerular inflammatory states.

scholarly journals Autoimmune mice make anti-Fc gamma receptor antibodies.

1990 ◽  
Vol 171 (5) ◽  
pp. 1581-1595 ◽  
Author(s):  
P Boros ◽  
J M Chen ◽  
C Bona ◽  
J C Unkeless
Keyword(s):  
Affinity Chromatography ◽  
Mouse Strain ◽  
Immune Complexes ◽  
Mesangial Cells ◽  
Fc Gamma Receptor ◽  
Gamma Receptor ◽  
Soluble Immune Complexes ◽  
Receptor Antibodies ◽  
Normal Macrophage

We demonstrate, using a recombinant truncated Fc gamma RII molecule as a probe, the presence of anti-Fc gamma R antibodies in several strains of autoimmune mice. Affinity chromatography on a truncated Fc gamma R column of pooled sera from aged NZB females resulted in isolation of 16 micrograms of IgM per ml of serum, approximately 2% of the total IgM; no anti-Fc gamma R IgM was found in sera from C58/J mice. Mice with high titers of anti-Fc gamma R IgM also had anti-Fc gamma R IgG. Affinity-purified anti-Fc gamma R IgG bound to Fc gamma R-bearing cells. A good correlation was found between the presence of anti-Fc gamma R Ig and impaired phagocytosis of immune complexes in autoimmune strains such as NZB or NZB/NZW F1. Sera with high titers of anti-Fc gamma R Ig from NZB and motheaten mice inhibited the binding of soluble immune complexes. Furthermore, BXSB, a lupus-prone mouse strain that does not produce anti-Fc gamma R Ig, shows normal macrophage binding and phagocytosis of immune complexes. A set of four IgM mAbs that bind to Fc gamma R was identified. These antibodies were polyspecific; some were directed against DNA, and others recognized a wide variety of antigens including histones, thyroglobulin, and transferrin, but all anti-Fc gamma R IgM antibodies effectively inhibited the binding of IgG1 anti-DNP/DNP20BSA complexes to J774 macrophages. The role of anti-Fc gamma R Ig in autoimmunity remains to be established. It may act to crosslink and activate Fc gamma Rs on neutrophils, macrophages, NK, and mesangial cells, or it may desensitize Fc gamma R function of Fc gamma R-bearing cells.

scholarly journals Homology cloning of rat 72 kDa type IV collagenase: cytokine and second-messenger inducibility in glomerular mesangial cells

1993 ◽  
Vol 291 (2) ◽  
pp. 441-446 ◽  
Author(s):  
H P Marti ◽  
L McNeil ◽  
M Davies ◽  
J Martin ◽  
D H Lovett
Keyword(s):  
Phorbol Ester ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Second Messenger ◽  
Tnf Alpha ◽  
Glomerular Mesangial Cells ◽  
Pcr Cloning ◽  
Type Iv Collagenase ◽  
Necrosis Factor Alpha ◽  
Type Iv

Glomerular mesangial cells (MC) play a central role in the synthesis and turnover of the glomerular extracellular matrix. Prior studies [Davies, Thomas, Martin and Lovett (1988) Biochem. J. 251, 419-425; Martin, Davies, Thomas and Lovett (1989) Kidney Int. 36, 790-801] have characterized at the protein level a 72 kDa type IV collagenase that is secreted by cultured human and rat MC. While exposure of most cell types to interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha) or phorbol ester has little or even an inhibitory effect on 72 kDa type IV collagenase secretion, these factors significantly increased the synthesis of this enzyme by rat MC. Given this divergent pattern of expression, a homology-based PCR cloning strategy using rat MC cDNA templates was employed to define at the molecular level the structure of the mesangial 72 kDa type IV collagenase. The nucleotide sequence within the open reading frame of the rat mesangial 72 kDa type IV collagenase cDNA diverges from the sequence of the human homologue by approx. 9%. The divergence in the 3′ untranslated region was much more extensive. Steady-state levels of the 3.1 kb transcript of the 72 kDa type IV collagenase were low or undetectable in resting MC, but were greatly stimulated following incubation with IL-beta, TNF-alpha or phorbol ester. None of these factors induced synthesis by MC of the closely related 92 kDa type IV collagenase. Synthesis by MC of the 72 kDa type IV collagenase was also induced by second-messenger analogues, including 8-bromo-cyclic AMP and forskolin. It is concluded that MC regulate the expression of this enzyme in an unusual, tissue-specific fashion. Cytokine and second-messenger inducibility may contribute to the enhanced expression of the enzyme during glomerular inflammatory disorders.

Interleukin 1 activates jun N-terminal kinases JNK1 and JNK2 but not extracellular regulated MAP kinase (ERK) in human glomerular mesangial cells

FEBS Letters ◽  
1996 ◽  
Vol 394 (3) ◽  
pp. 273-278 ◽  
Author(s):  
Peter Uciechowski ◽  
Jeremy Saklatvala ◽  
Juliane von der Ohe ◽  
Klaus Resch ◽  
Martha Szamel ◽  
...  
Keyword(s):  
Map Kinase ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Glomerular Mesangial Cells ◽  
Human Glomerular Mesangial Cells

scholarly journals Modulatory role of platelet-derived growth factor on cytokine-induced nerve growth factor synthesis in rat glomerular mesangial cells

1995 ◽  
Vol 312 (3) ◽  
pp. 707-711 ◽  
Author(s):  
K M A Plüss ◽  
J Pfeilschifter ◽  
H Mühl ◽  
A Huwiler ◽  
C Boeckh ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Platelet Derived Growth Factor ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Glomerular Mesangial Cells ◽  
Peripheral Tissues ◽  
Nerve Growth

Recent evidence indicates that cytokines are potent inducers of nerve growth factor (NGF) expression in peripheral tissues and in brain. Cultured rat glomerular mesangial cells respond to interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) by increased NGF synthesis. We found that co-stimulation of rat glomerular mesangial cells with platelet-derived growth factor (PGDF-BB) and IL-1 beta/TNF-alpha significantly augments the IL-1 beta/TNF-alpha-induced NGF mRNA levels and NGF synthesis. In contrast, preincubation with PDGF-BB drastically reduces NGF gene expression and NGF protein synthesis in response to IL-1 beta/TNF-alpha stimulation. Thus our results indicate that PDGF-BB is a potent modulator of cytokine-induced NGF expression; its precise action is critically depending on the time at which the PDGF receptor is activated.

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