Stimulus-specific 1,25(OH)2D3 modulation of TNF and IL-1-beta gene expression in human peripheral blood mononuclear cells and monocytoid cell lines.
It is known that 1,25(OH)2D3 inhibits IL-2, IFN-gamma, and GM-CSF mRNA accumulation in activated T cells. While 1,25(OH)2D3 enhances macrophage competence, its effect on cytokine gene expression in monocytes is less well defined. Using Northern blot analysis, we examined the effect of 1,25(OH)2D3 pretreatment on IL-1 beta and TNF gene expression in LPS- and PHA-stimulated human PBMNC and several human myeloid cell lines (U937 and THP1). In PBMNC, preincubation had no effect on the steady-state level of LPS-induced TNF or IL-1 beta mRNA. When PHA was used to stimulate pretreated PBMNC, a 60-80% inhibition of TNF mRNA levels was observed. There was no effect on IL-1 beta mRNA. In U937 cells, 1,25(OH)2D3 preincubation resulted in a 4-fold increase in the level of TNF and IL-1 beta mRNA levels. Pretreatment had no effect on TNF or IL-1 beta gene expression in THP1 cells. The observation that PHA-induced TNF gene expression is modulated by 1,25(OH)2D3 is novel. Possible mechanisms by which 1,25(OH)2D3 preincubation may influence mitogen-specific inducible cytokine gene expression in different cell types are discussed.
Blifeld
C
C
Renal Immunology Laboratory, Ahmanson Pediatric Center, Cedars-Sinai Medical Center, UCLA School of Medicine 90048.
Prehn
J L
JL
Jordan
S C
SC
D015152:Blotting, Northern; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D007375:Interleukin-1; D008934:Mitogens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002117:Calcitriol