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Inhibition of cytokine secretion from adipocytes by 1,25‐dihydroxyvitamin D 3 via the NF‐κB pathway
Author(s) -
Mutt Shivaprakash J.,
Karhu Toni,
Lehtonen Siri,
Lehenkari Petri,
Carlberg Carsten,
Saarnio Juha,
Sebert Sylvain,
Hyppönen Elina,
Järvelin MarjoRitta,
Herzig KarlHeinz
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-210880
Subject(s) - medicine , endocrinology , secretion , adipose tissue , western blot , cytokine , stromal cell , adipocyte , nf κb , chemistry , inflammation , tumor necrosis factor alpha , lipopolysaccharide , iκbα , biology , microbiology and biotechnology , biochemistry , gene
Adipose tissue inflammation is an important pathological process in obese people, associated with diabetes and cardiovascular disease. We hypothesized that 1,25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] inhibits cytokine secretion from adipocytes via direct inhibition of transcription factor nuclear factor‐κB (NF‐κB). We utilized two different human models. Bone marrow‐derived human mesenchymal stromal cells (hMSCs) differentiated into adipocytes, and adipocytes isolated from biopsies stimulated with lipopolysaccharide (LPS) were treated with or without 1,25(OH) 2 D 3 . Expression and secretion of interleukin‐6 (IL‐6) were measured by quantitative RT‐PCR analysis and ELISA. Assessment of NF‐κB nuclear translocation, DNA binding activity was performed by immunofluorescence (IF) and electrophoretic mobility assay (EMSA). Inhibitor κB (IκB) and its phosphorylation were detected by Western blot (WB) analysis. Simultaneous 1,25(OH) 2 D 3 cotreatment significantly reduced LPS‐stimulated (10 ng/ml) IL‐6 secretion dose dependently by 15% at 10 –10 M and 26% at 10 –7 M ( P <0.05) in hMSCs, while preincubation with 1,25(OH) 2 D 3 (10 –7 M) for 24 h reduced IL‐6 secretion by 24 and 35% ( P <0.001) and mRNA levels by 34 and 30% ( P <0.05) in hMSCs and isolated adipocytes, respectively. 1,25(OH) 2 D 3 suppressed LPS‐stimulated IκB phosphorylation‐mediated NF‐κB translocation into the nucleus were evident from WB, IF, and EMSA. 1,25(OH) 2 D 3 inhibits LPS‐stimulated IL‐6 secretion in two human adipocyte models via interference with NF‐κB signaling.—Mutt, S. J., Karhu, T., Lehtonen, S., Lehenkari, P., Carlberg, C., Saarnio, J., Sebert, S., Hyppönen, E., Järvelin, M.‐R., Herzig, K.‐H. Inhibition of cytokine secretion from adipocytes by 1,25‐dihydroxyvitamin D 3 via the NF‐κB pathway. FASEB J. 26, 4400–4407 (2012). www.fasebj.org