Effects of vitamin D3 on expression of tumor necrosis factor-alpha and chemokines by monocytes.
The association between vitamin D deficiency and asthma epidemic has been recognized. Tumor necrosis factor (TNF)-alpha and chemokines play important roles in pathogenesis of asthma. However, whether vitamin D has immunoregulatory function on TNF-alpha and chemokines expression in human monocytes is still unknown. The human monocytic cell line, THP-1 cells and human primary monocytes were pretreated with various concentration of 1alpha,25-(OH)(2)D(3) for 2 h before stimulation with lipopolysaccharide (LPS). Supernatants were collected 24 or 48 h after LPS stimulation. The levels of TNF-alpha, interferon-inducible protein 10 (IP-10)/CXCL10 (the Th1-related chemokine), macrophage-derived chemokine (MDC)/ CCL22 (the Th2-related chemokine), and interleukin 8 (IL-8)/CXCL8 (the neutrophil chemoattractant) were measured by ELISA. 1alpha,25-(OH)(2)D(3) could significantly suppress TNF-alpha and IP-10 expression in LPS-stimulated THP-1 and human primary monocytes. However, 1alpha,25-(OH)(2)D(3), especially in higher concentration, could significantly enhance MDC expression. 1alpha,25-(OH)(2)D(3) had no significant effects on IL-8 expression. We found 1alpha,25-(OH)(2)D(3) could significantly suppress TNF-alpha and Th1-related chemokine IP-10, which both play important roles in pathogenesis of severe refractory asthma and autoimmune diseases. However, 1alpha,25-(OH)(2)D(3) enhanced Th2-related chemokine MDC, which may result in Th2 inflammatory cell recruitment and thus adversely affect asthmatic patients. Although vitamin D has potential utility in the treatment of asthma and autoimmune diseases, excessive use of vitamin D may not be suitable in patients with Th2 allergic diseases.
Kuo
Yu-Ting
YT
Dept. of Pediatrics, Kaohsiung Medical Univ. Hospital, Kaohsiung, Taiwan.
Kuo
Chang-Hung
CH
Lam
Ka-Pan
KP
Chu
Yu-Te
YT
Wang
Wei-Li
WL
Huang
Ching-Hua
CH
Hung
Chih-Hsing
CH
D001249:Asthma / Q000453:epidemiology / Q000276:immunology; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000276:immunology; D002117:Calcitriol / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D054422:Chemokine CCL22 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D002762:Cholecalciferol / Q000502:physiology*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009994:Osmolar Concentration; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation; D014808:Vitamin D Deficiency / Q000276:immunology / Q000503:physiopathology
C515482:CCL22 protein, human; C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; D018925:Chemokines; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002762:Cholecalciferol; D002117:Calcitriol