Dept. of Pediatrics, Kaohsiung Medical Univ. Hospital, Kaohsiung, Taiwan.
J Food Sci. 2010 Aug 1;75(6):H200-4. doi: 10.1111/j.1750-3841.2010.01704.x.
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.
维生素 D 缺乏与哮喘流行之间的关联已得到确认。肿瘤坏死因子 (TNF)-α 和趋化因子在哮喘发病机制中发挥重要作用。然而，维生素 D 是否对人单核细胞中 TNF-α 和趋化因子的表达具有免疫调节作用仍不清楚。本研究用不同浓度的 1α,25-(OH)2D3 预处理人单核细胞株 THP-1 细胞和人原代单核细胞 2 h，然后用脂多糖 (LPS) 刺激。LPS 刺激 24 或 48 h 后收集上清液。用 ELISA 检测 TNF-α、干扰素诱导蛋白 10 (IP-10)/CXCL10（Th1 相关趋化因子）、巨噬细胞来源趋化因子 (MDC)/CCL22（Th2 相关趋化因子）和白细胞介素 8 (IL-8)/CXCL8（中性粒细胞趋化因子）的水平。1α,25-(OH)2D3 可显著抑制 LPS 刺激的 THP-1 和人原代单核细胞中 TNF-α和 IP-10 的表达。然而，1α,25-(OH)2D3，尤其是高浓度时，可显著增强 MDC 的表达。1α,25-(OH)2D3 对 IL-8 的表达无明显影响。我们发现 1α,25-(OH)2D3 可显著抑制 TNF-α和 Th1 相关趋化因子 IP-10 的表达，它们在严重难治性哮喘和自身免疫性疾病的发病机制中都发挥重要作用。然而，1α,25-(OH)2D3 增强了 Th2 相关趋化因子 MDC 的表达，这可能导致 Th2 炎性细胞的募集，从而对哮喘患者产生不利影响。虽然维生素 D 在治疗哮喘和自身免疫性疾病方面具有潜在的应用价值，但在 Th2 过敏疾病患者中过度使用维生素 D 可能并不合适。
