1 alpha,25-dihydroxyvitamin D3 suppresses interleukin-1beta-induced interleukin-8 production in human whole blood: an involvement of erythrocytes in the inhibition.
Interleukin (IL)-8, which is involved in inflammatory responses, is produced by a variety of cell types, monocytes/macrophages and neutrophils, in response to inflammatory stimuli including lipopolysaccharide, IL-1, and tumor necrosis factor alpha. Here we report the inhibitory effects of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) on IL-8 production in human whole blood culture. 1,25(OH)2D3 inhibited only the late phase of the biphasic IL-8 production in lipopolysaccharide-stimulated human whole blood. It also effectively inhibited IL-8 production induced by IL-lbeta compared with that induced by tumor necrosis factor alpha. IL-8 mRNA expression in IL-lbeta-stimulated whole blood was found to require de novo protein synthesis. Although monocytes were found to be mainly responsible for IL-1beta-induced IL-8 production in whole blood, 1,25(OH)2D3 inhibited IL-8 production by isolated mononuclear cells only marginally. The inhibitory effect of 1,25(OH)2D3 on mononuclear cells was restored by adding erythrocytes. These results suggest that erythrocytes play a role in mediating the inhibitory effects of 1,25(OH)2D3 on IL-8 production in IL-1beta-stimulated whole blood.
Takahashi
Katsushi
K
Pharmaceuticals Development Laboratories, Teijin Institute for Bio-Medical Research, Hino, Tokyo, Japan. kat.takahashi@teijin.co.jp
Horiuchi
Hideki
H
Ohta
Tomohiro
T
Komoriya
Keiji
K
Ohmori
Hitoshi
H
Kamimura
Takashi
T
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood*; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D002120:Calcium Channel Agonists; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D002117:Calcitriol