Schling Petra, Rudolph Christian, Heimerl Susanne, Fruth Sabine, Schmitz Gerd
Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
Cytokine. 2006 Mar 7;33(5):239-45. doi: 10.1016/j.cyto.2006.02.007. Epub 2006 Mar 31.
Tumor necrosis factor alpha (TNFalpha) is a potent proinflammatory cytokine also involved in cellular differentiation processes. TNFalpha and both of its receptors (TNFR1 and TNFR2) can be co-expressed on the same cell, allowing for local signaling. This study has examined the expression of all components necessary for autocrine cytokine regulation during human hematopoietic, epithelial, and mesenchymal models of cellular differentiation. Macrophage and dendritic differentiation of human peripheral blood monocytes decreased their TNFalpha and TNFR2 expression while increasing the TNFR1 mRNA. In colon epithelial cell lines (HT-29 and Caco-2) TNFalpha-, TNFR1-, and TNFR2-expression was decreased upon differentiation. No changes, however, were seen during human skin keratinocyte differentiation. TNFR1 expression was unchanged in all three mesenchymal lineages (adipogenesis, chondrogenesis, osteogenesis) tested. Differentiation decreases the TNFalpha message in adipocytes and the TNFR2 mRNA in adipocytes and osteocytes. Our results demonstrate that there is no general principle for TNFalpha signaling during conversion of cells from progenitor to a more differentiated phenotype. Paracrine signaling by TNFalpha to orchestrate different cell types during tissue development and remodeling, therefore, probably overrides the autocrine regulation of differentiation by TNFalpha. Non-signaling TNF-receptors may protect chondrocytes and osteocytes from the anti-differentiation effects of local TNFalpha production.
肿瘤坏死因子α（TNFα）是一种强效促炎细胞因子，也参与细胞分化过程。TNFα及其两种受体（TNFR1和TNFR2）可在同一细胞上共表达，从而实现局部信号传导。本研究检测了人类造血、上皮和间充质细胞分化模型中自分泌细胞因子调节所需的所有成分的表达。人类外周血单核细胞向巨噬细胞和树突状细胞的分化降低了其TNFα和TNFR2的表达，同时增加了TNFR1 mRNA的表达。在结肠上皮细胞系（HT - 29和Caco - 2）中，分化后TNFα、TNFR1和TNFR2的表达均降低。然而，在人类皮肤角质形成细胞分化过程中未见变化。在所测试的所有三种间充质谱系（脂肪生成、软骨生成、骨生成）中，TNFR1的表达均未改变。分化降低了脂肪细胞中的TNFα信息以及脂肪细胞和骨细胞中的TNFR2 mRNA。我们的结果表明，在细胞从祖细胞转变为更分化表型的过程中，不存在TNFα信号传导的一般规律。因此，在组织发育和重塑过程中，TNFα通过旁分泌信号协调不同细胞类型，这可能会优先于TNFα对分化的自分泌调节。无信号传导的TNF受体可能保护软骨细胞和骨细胞免受局部TNFα产生的抗分化作用。
