Upregulation of interleukin-1β production by 1,25-dihydroxyvitamin D(3) in activated human macrophages.
1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) plays important roles in the immune system. In contrast to its well known function in the adaptive immune system, much less is known about the immunoregulatory effects of 1,25(OH)(2)D(3) in the innate immune system, especially on activated human macrophages. Here we found that 1,25(OH)(2)D(3) strongly stimulated the production of interleukin-1β (IL-1β) in PMA-differentiated U937 cells and human monocyte-derived macrophages treated with lipopolysaccharide (LPS) or PMA. In this study, Erk1/2 appeared to mediate 1,25(OH)(2)D(3)-induced expression of IL-1β. Parallel to the increased production of IL-1β, 1,25(OH)(2)D(3) increased the expression and phosphorylation of the CCAAT enhancer-binding protein β (C/EBPβ), which is one of the key transcriptional regulatory factors for IL-1β transcription. These results suggest that 1,25(OH)(2)D(3) may function as a proinflammatory molecule in inflammatory macrophages.
Lee
Bit-Na-Ra
BN
The Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea.
Kim
Tae-Hwan
TH
Jun
Jae-Bum
JB
Yoo
Dae-Hyun
DH
Woo
Jin-Hyun
JH
Choi
Sung Jae
SJ
Lee
Young Ho
YH
Song
Gwan Gyu
GG
Kim
Yongjin
Y
Lee
Ji Young
JY
Sohn
Jeongwon
J
Ji
Jong Dae
JD
D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology; D010766:Phosphorylation / Q000187:drug effects; D020871:RNA Stability / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
D022782:CCAAT-Enhancer-Binding Protein-beta; D053583:Interleukin-1beta; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D048049:Extracellular Signal-Regulated MAP Kinases