Neuropoietic cytokines and activin A differentially regulate the phenotype of cultured sympathetic neurons.

A number of cytokines sharing limited sequence homology have been grouped as a family because of partially overlapping biological activities, receptor subunit promiscuity, and the prediction of a shared secondary structure. Since several of these cytokines regulate gene expression and cell number in the nervous and hematopoietic systems, this specific group is termed the neuropoietic cytokine family. Using a reverse transcription-polymerase chain reaction-based assay system for monitoring the expression of multiple phenotypic markers in cultured sympathetic neurons, we present further evidence that, in addition to cholinergic differentiation factor/leukemia inhibitory factor and ciliary neurotrophic factor, oncostatin M, growth promoting activity, interleukin 6, and interleukin 11 belong in this family. In addition, one member of the transforming growth factor beta superfamily, activin A, shares a selective overlap with the neuropoietic family in the spectrum of neuropeptides that it induces in sympathetic neurons. The particular neuropeptides induced by activin A, however, demonstrate that the activity of this cytokine is distinct from that of the neuropoietic family. Twenty-six other cytokines and growth factors were without detectable activity in this assay. IMAGES:

众多序列同源性有限的细胞因子，因生物学活性部分重叠、受体亚基存在通用性，且预测具有共同的二级结构，被归为同一家族。由于该类细胞因子中的多种可调控神经系统与造血系统的基因表达及细胞数量，故此特定类群被命名为神经造血细胞因子家族（neuropoietic cytokine family）。本研究采用基于逆转录聚合酶链反应的检测体系，对培养的交感神经元中多种表型标志物的表达进行监测，据此提供了进一步证据：除胆碱能分化因子/白血病抑制因子（cholinergic differentiation factor/leukemia inhibitory factor）与睫状神经营养因子（ciliary neurotrophic factor）外，制瘤素M（oncostatin M）、促生长活性物质、白细胞介素6（interleukin 6）及白细胞介素11（interleukin 11）亦隶属于该家族。此外，转化生长因子β超家族（transforming growth factor beta superfamily）的一员——激活素A（activin A），在其诱导交感神经元产生的神经肽谱中，与神经造血细胞因子家族存在选择性重叠。然而，激活素A所诱导的特定神经肽表明，该细胞因子的活性与神经造血细胞因子家族存在显著差异。其余26种细胞因子与生长因子在本检测体系中均未检测到相关活性。IMAGES: