Kreft B, Brzoska S, Doehn C, Daha M R, Van Der Woude F J, Sack K
Department of Internal Medicine, Medical University of Lübeck, Lübeck, Germany.
J Urol. 1996 Apr;155(4):1448-53.
Beside its role in calcium and phosphorus metabolism, 1,25-dihydroxycholecalciferol (1,25-D3) exerts multiple effects on cytokine and major histocompatibility complex (MHC) class II expression in monocytes and lymphocytes. In different renal diseases tubular epithelial cells express MHC class II molecules and cell adhesion molecules,, such as intracellular adhesion molecule-1 (ICAM-1). Therefore, modulation of MHC class II and ICAM-1 expression in renal tubular epithelial cells by 1,25-D3 may be relevant to lymphocyte adhesion to tubular epithelial cells and immune mediated renal injury. However, the expression of MHC class II antigens and cellular adhesion molecules by renal tubular epithelial cells in response to 1,25-D3 has not been investigated.
We generated human renal tubular epithelial cells and SV40 transfected tubular epithelial cells to investigate immune modulation of 1,25 on renal epithelial cells. Major histocompatibility complex class II molecules and ICAM-1 were detected by a specific enzyme linked immunoassay.
We found a dose-dependent increase of both constitutive and induced MHC class II and ICAM-1 expression in tubular epithelial cells stimulated with 1,25-D3. Dose-dependent stimulation of MHC class II and ICAM-1 expression was not restricted to primary human renal tubular epithelial cells but was also detected in SV40 transfected cells.
Expression of MHC class II and ICAM-1 is crucial for antigen presentation by and lymphocyte adhesion to renal tubular epithelial cells. Modulatory effects of 1,25-D3 on immune accessory function of renal tubular epithelial cells may be of clinical significance in renal diseases.
1,25 - 二羟胆钙化醇(1,25 - D3)除了在钙和磷代谢中发挥作用外,还对单核细胞和淋巴细胞中的细胞因子及主要组织相容性复合体(MHC)II类分子的表达产生多种影响。在不同的肾脏疾病中,肾小管上皮细胞表达MHC II类分子和细胞黏附分子,如细胞间黏附分子 - 1(ICAM - 1)。因此,1,25 - D3对肾小管上皮细胞中MHC II类分子和ICAM - 1表达的调节可能与淋巴细胞黏附于肾小管上皮细胞以及免疫介导的肾损伤有关。然而,肾小管上皮细胞对1,25 - D3反应时MHC II类抗原和细胞黏附分子的表达尚未得到研究。
我们培养了人肾小管上皮细胞和SV40转染的肾小管上皮细胞,以研究1,25对肾上皮细胞的免疫调节作用。通过特异性酶联免疫测定法检测主要组织相容性复合体II类分子和ICAM - 1。
我们发现,在用1,25 - D3刺激的肾小管上皮细胞中,组成性和诱导性的MHC II类分子和ICAM - 1表达均呈剂量依赖性增加。MHC II类分子和ICAM - 1表达的剂量依赖性刺激不仅限于原代人肾小管上皮细胞,在SV40转染细胞中也能检测到。
MHC II类分子和ICAM - 1的表达对于肾小管上皮细胞的抗原呈递及淋巴细胞黏附至关重要。1,25 - D3对肾小管上皮细胞免疫辅助功能的调节作用在肾脏疾病中可能具有临床意义。