Interleukin-1 regulates cytokine gene expression in human mesangial cells through the interleukin-1 receptor type 1.
We have recently shown that interleukin-1 is a potent stimulus of gene expression and production of leukocyte chemotactic factors, colony-stimulating factors, and interleukin-6 in human mesangial cells in culture. Here, we sought to determine whether interleukin-1 induces its own gene expression in human mesangial cells. Interleukin-1 mRNA levels were quantitated by Northern blot analysis with total cellular RNAs isolated from human mesangial cells exposed for 6 h to medium alone or in the presence of human recombinant interleukin-1 beta (1 to 100 ng/mL). Interleukin-1 induced interleukin-1 mRNA expression in a dose-dependent manner. An additional finding of this study was that human mesangial cells constitutively express the 80 kd interleukin-1 receptor type 1 gene. When human mesangial cells were exposed to interleukin-1, interleukin-1 receptor expression was not modified. Similarly, other stimuli like tumor necrosis factor, transforming growth factor beta, or interleukin-6 did not modulate interleukin-1 receptor expression. Recombinant interleukin-1 receptor antagonist blocked the interleukin-1 mRNA as well as interleukin-6 and interleukin-8 mRNA accumulation induced by interleukin-1 beta. Lipopolysaccharide, which is a known stimulus for interleukin-1 transcription in several cell types, also induced interleukin-1 mRNA accumulation, thus indicating that lipopolysaccharide mediates interleukin-1 gene activation in human mesangial cells through an interleukin-1-independent pathway. These data support the pivotal role of interleukin-1 in regulating mesangial cell cytokine genes and may be taken to indicate the existence of an interleukin-1-mediated positive feedback loop that might control the secretion of active cytokines within the glomeruli when an immunological or inflammatory injury takes place.
Zoja
C
C
Mario Negri Institute for Pharmacological Research, Ospedali Riuniti di Bergamo, Italy.
Bettoni
S
S
Morigi
M
M
Remuzzi
G
G
Rambaldi
A
A
D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism; D017472:Receptors, Interleukin-1
D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1