Godot V, Garcia G, Capel F, Arock M, Durand-Gasselin I, Asselin-Labat M L, Emilie D, Humbert M
INSERM U764, Université Paris-Sud 11, Clamart, France.
Allergy. 2006 Jul;61(7):886-90. doi: 10.1111/j.1398-9995.2006.01065.x.
Glucocorticoids (GCs) decrease tissue mast cell (MC) number and prevent their activation via their high-affinity IgE receptor. Glucocorticoid-induced leucine zipper (GILZ) is one of the GC-induced genes, which inhibits the functions of the transcriptional activators AP-1 and NF-kappaB. GILZ appears to be a critical actor in the anti-inflammatory and immunosuppressive effects of GCs in human T lymphocytes, macrophages and dendritic cells.
We investigated whether GILZ was produced by human MCs and whether GILZ synthesis was stimulated by GCs. We also investigated whether GILZ production was modulated by (i) IL-10, because of its common immunosuppressive properties with GCs, (ii) histamine because of its pro-inflammatory properties and (iii) IL-4 and IL-5 because of their ability to favour MC survival and proliferation with SCF.
The human MC lines HMC-1 5C6 and LAD-2, and cord blood-derived MCs (CB-MCs) were cultured alone or in the presence of GCs, IL-10, histamine, IL-4 or IL-5. The expression of GILZ was evaluated by using RT-PCR, Western blotting or immunocytochemistry.
We found that human MC lines and CB-MCs constitutively produce GILZ. We also show that GCs and IL-10 stimulate GILZ production by human MCs. Our present results indicate that histamine, IL-4 and IL-5 alone or in combination with SCF do not downregulate GILZ production by MCs.
These results show that GCs and IL-10 stimulate GILZ production by human MCs. As GILZ mediates anti-inflammatory effects of GCs in immune cells, we speculate that GILZ could account for the deactivation of MCs by GCs and IL-10.
糖皮质激素（GCs）可减少组织肥大细胞（MC）数量，并通过其高亲和力IgE受体阻止MC激活。糖皮质激素诱导亮氨酸拉链蛋白（GILZ）是GC诱导的基因之一，可抑制转录激活因子AP-1和核因子κB的功能。GILZ似乎是GCs在人T淋巴细胞、巨噬细胞和树突状细胞中发挥抗炎和免疫抑制作用的关键因子。
我们研究了人MCs是否产生GILZ，以及GCs是否刺激GILZ合成。我们还研究了GILZ的产生是否受以下因素调节：（i）IL-10，因其与GCs具有共同的免疫抑制特性；（ii）组胺，因其具有促炎特性；（iii）IL-4和IL-5，因其与干细胞因子（SCF）共同促进MC存活和增殖的能力。
人MC系HMC-1 5C6和LAD-2以及脐血来源的MCs（CB-MCs）单独培养或在GCs、IL-10、组胺、IL-4或IL-5存在的情况下培养。通过逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法或免疫细胞化学评估GILZ的表达。
我们发现人MC系和CB-MCs组成性地产生GILZ。我们还表明，GCs和IL-10刺激人MCs产生GILZ。我们目前的结果表明，组胺、IL-4和IL-5单独或与SCF联合使用不会下调MCs产生GILZ。
这些结果表明，GCs和IL-10刺激人MCs产生GILZ。由于GILZ介导GCs在免疫细胞中的抗炎作用，我们推测GILZ可能是GCs和IL-10使MCs失活的原因。
