Interleukin (IL)-1 and IL-4 synergistically stimulate NF-IL6 activity and IL-6 production in human mesangial cells.
BACKGROUND
While interleukin (IL)-4 inhibits pro-inflammatory cytokine expression by human monocytes, we have observed that it potentiates IL-6 production by IL-1-activated human mesangial cells (MC). To study the mechanism of this cell-type specific interaction between IL-1 and IL-4 in MC, we examined the effect of both cytokines on the activities of nuclear factor kappa B (NF-kappa B) and nuclear IL-6 NL-IL 6), transcription factors that are essential for IL-6 gene expression.


METHODS
We evaluated IL-6 synthesis, mRNA expression, and mRNA stability by ELISA, Northern analysis, and the actinomycin D method, respectively. Activities of NF-kappa B and NF-IL 6 were analyzed by gel shift assay.


RESULTS
IL-4 augmented the IL-1 stimulated IL-6 mRNA levels by about threefold without altering mRNA stability. IL-1 treatment rapidly induced the binding activity of NF-kappa B. In contrast, IL-4 did not affect basal and IL-1-induced NF-kappa B activities. Both IL-1 and IL-4 stimulated NF-IL6 activity as early as 30 minutes after treatment. When MC were treated with both cytokines together, marked activation of NF-IL6 was observed at five hours.


CONCLUSIONS
These results suggest that simultaneous activation of NF-kappa B and NF-IL6 is essential for IL-6 gene expression and that IL-1 and IL-4 cooperatively stimulate MC IL-6 production through their synergistic activation of NF-IL6.
Nakazato
Y
Y
Department of Internal Medicine, School of Medicine, Keio University, Saitama, Japan.
Hayashida
T
T
Kanno
Y
Y
Sasamura
H
H
Okada
H
H
Suzuki
H
H
Saruta
T
T
D022762:CCAAT-Enhancer-Binding Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D005920:Glomerular Mesangium / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics*; D016328:NF-kappa B / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D015847:Interleukin-4