Aberrant regulation of IL-1 expression in macrophages from young autoimmune-prone mice.
Aberrant regulation of IL-1 expression in macrophages from young autoimmune-prone mice.
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DOI：
10.4049/jimmunol.145.10.3231
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发表时间：
1990-11
影响因子：
4.4
通讯作者：
Raymond P. Donnelly;J. Levine;D. Hartwell;Gyorgy Frendl;Matthew J. Fenton;D. Beller
中科院分区：
文献类型：
--
作者：
Raymond P. Donnelly;J. Levine;D. Hartwell;Gyorgy Frendl;Matthew J. Fenton;D. Beller
IL-1是由许多细胞类型产生的多功能免疫调节多肽。因为活化的巨噬细胞是IL-1的主要来源，并且还与自身免疫性疾病的发病机制有关，所以我们研究了几种自身免疫易感小鼠品系中IL-1表达的调节。来源于自身免疫易感菌株MRL/lpr、MRL/+、NZB和NZB/W F1以及NZW的腹膜巨噬细胞显示IL-1的瞬时表达，这与包括A. Thy、A/J、B10、B10.A、B10.D2、C57BL/6、BALB/c和C3H/HeN。来自自身免疫易感小鼠的巨噬细胞对IL-1的下调并不归因于固有缺陷的信号转导，因为来自正常和自身免疫易感菌株的巨噬细胞显示出实质性的细胞相关和分泌的IL-1的初始水平。然而，在培养的前2至3天，来自自身免疫易感小鼠的巨噬细胞变得对IL-1的诱导和维持都逐渐难治，这种模式与IL-1 α和β mRNA水平的变化相关。这些自身免疫易感株巨噬细胞IL-1表达的逐步减少不是由于一般代谢或活力的降低，因为细胞表面抗原（包括MHC I类和II类Ag和LFA-1）的表达与对照巨噬细胞相当。由于IL-1在多种细胞谱系的体内平衡中起关键作用，来自自身免疫易感株的巨噬细胞的IL-1（以及可能的其他细胞因子）的缺陷表达和维持可能导致在这些小鼠中发展的免疫失调。或者，细胞因子失调可能不会直接导致疾病，而是反映了与特定信号转导或基因调控途径相关的更基本的缺陷。
IL-1 is a multifunctional, immunoregulatory polypeptide produced by many cell types. Because activated macrophages are a major source of IL-1 and have also been implicated in the pathogenesis of autoimmune disease, we investigated the regulation of IL-1 expression in several autoimmune-prone strains of mice. Peritoneal macrophages derived from the autoimmune-prone strains MRL/lpr, MRL/+, NZB, and NZB/W F1, as well as NZW, displayed transient expression of IL-1 in contrast to the stable expression characteristic of control normal strains including A. Thy, A/J, B10, B10.A, B10.D2, C57BL/6, BALB/c, and C3H/HeN. The down-regulation of IL-1 by macrophages from the autoimmune-prone mice was not attributable to inherently defective signal transduction because macrophages from both the normal and autoimmune-prone strains displayed substantial initial levels of cell-associated and secreted IL-1. However, during the first 2 to 3 days in culture, macrophages from autoimmune-prone mice became progressively refractory to both induction and maintenance of IL-1, a pattern that correlated with changes in the levels of IL-1 alpha and beta mRNA. The progressive reduction in IL-1 expression by macrophages from these autoimmune-prone strains was not due to a reduction in general metabolism or viability, because expression of cell surface antigens, including MHC class I and II Ag and LFA-1, was comparable to that of control macrophages. Because IL-1 plays a critical role in the homeostasis of a variety of cell lineages, defective expression, and maintenance of IL-1 (and perhaps other cytokines) by macrophages from the autoimmune-prone strains may contribute to the immune dysregulation that develops in these mice. Alternatively, cytokine dysregulation might not contribute directly to disease, but rather reflect a more basic defect related to specific signal transducing or gene regulatory pathways.