da Cunha A, Jefferson J A, Jackson R W, Vitković L
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
J Neuroimmunol. 1993 Jan;42(1):71-85. doi: 10.1016/0165-5728(93)90214-j.
Transforming growth factor beta-1 (TGF-beta 1) immunoreactive product (IRP) has recently been detected in autopsied brains of individuals who died with central nervous system diseases and/or fever but not in normal individuals or in normal rodent brain. However, the mechanism(s) of induction of TGF-beta 1 in brain and the identity of cells expressing TGF-beta 1 need to be understood before a role, if any, for this potent pleiotropic cytokine in neuropathogenesis can be discerned. Towards this end we determined that IL-1 stimulated the production of TGF-beta 1 IRP in cells and TGF-beta 1 activity in culture fluids of all glial cells, astrocytes, microglial cells, and oligodendrocytes, derived from neonatal rat cortex and grown in cell type-enriched cultures. TGF-beta 1 production in vitro varied with the cell type and isoform of IL-1. Oligodendrocytes produced the most and astrocytes the least amount of TGF-beta 1. IL-1 alpha stimulated TGF-beta 1 production in all glial cell types, whereas IL-1 beta did not. In vivo, TGF-beta 1 IRP was detected in human tissues from cerebral frontal cortex and subcortical white matter only when interleukin-1 (IL-1) was elevated in the same tissues. Moreover, the amount of detectable TGF-beta 1 was positively correlated with the amount of detectable IL-1 (rho = 0.605; P = 0.003), as determined by morphometry. Double-labelling of cells for their phenotypic markers and expression of TGF-beta 1 indicated that all glial cells, but not neurons, expressed TGF-beta 1. IL-1 alpha and IL-1 beta IRPs were also detected in all three glial cell types, most frequently in astrocytes and least frequently in microglial cells. The cells containing both cytokine IRPs were also detected. These results indicate that TGF-beta 1 may be induced by IL-1 in all glial cells of the frontal cortex, by both autocrine and paracrine mechanisms.
转化生长因子β-1（TGF-β1）免疫反应产物（IRP）最近在死于中枢神经系统疾病和/或发热的个体的尸检大脑中被检测到，但在正常个体或正常啮齿动物大脑中未被检测到。然而，在确定这种强效多效细胞因子在神经发病机制中是否起作用（如果有作用的话）之前，需要了解大脑中TGF-β1的诱导机制以及表达TGF-β1的细胞类型。为此，我们确定白细胞介素-1（IL-1）刺激了源自新生大鼠皮质并在细胞类型丰富的培养物中生长的所有神经胶质细胞、星形胶质细胞、小胶质细胞和少突胶质细胞的细胞中TGF-β1 IRP的产生以及培养液中TGF-β1的活性。体外TGF-β1的产生因细胞类型和IL-1的亚型而异。少突胶质细胞产生的TGF-β1最多，星形胶质细胞产生的最少。IL-1α刺激所有神经胶质细胞类型产生TGF-β1，而IL-1β则没有。在体内，仅当同一组织中白细胞介素-1（IL-1）升高时，才在大脑额叶皮质和皮质下白质的人体组织中检测到TGF-β1 IRP。此外，通过形态计量学确定，可检测到的TGF-β1量与可检测到的IL-1量呈正相关（ρ = 0.605；P = 0.003）。对细胞进行表型标记和TGF-β1表达的双重标记表明，所有神经胶质细胞而非神经元表达TGF-β1。在所有三种神经胶质细胞类型中也检测到了IL-1α和IL-1β IRP，最常见于星形胶质细胞，最不常见于小胶质细胞。还检测到了同时含有两种细胞因子IRP的细胞。这些结果表明，TGF-β1可能由IL-1通过自分泌和旁分泌机制在额叶皮质的所有神经胶质细胞中诱导产生。
