Modulation of MMP‐2 (gelatinase A) and MMP‐9 (gelatinase B) by interferon‐γ in a human salivary gland cell line

Modulation of MMP‐2 (gelatinase A) and MMP‐9 (gelatinase B) by interferon‐γ in a human salivary gland cell line
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干扰素-γ 对人唾液腺细胞系中 MMP-2(明胶酶 A)和 MMP-9(明胶酶 B)的调节

DOI:
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发表时间:
1997
影响因子:
5.6
通讯作者:
B. Baum
B. Baum
中科院分区:
生物学2区
文献类型:
--
作者:
A. Wu;R. Lafrenie;C. Park;W. Apinhasmit;Z. J. Chen;H. Birkedal‐Hansen;Kenneth M. Yamada;W. Stetler;B. Baum

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明胶酶已被证明受到许多细胞因子和生长因子的调节,并通过组织破坏参与某些自身免疫性疾病的发病机制。干燥综合征 (SS) 患者的唾液腺微环境中存在高水平的多种细胞因子,包括 IFN-γ 和 TNF-α。这些细胞因子如何导致这种疾病的发病机制尚不清楚。我们假设 IFN-γ 联合或不联合 (±) TNF-α 可能通过调节基质金属蛋白酶 (MMP) 水平在 SS 的发病机制中发挥作用。本研究探讨了 IFN-γ 和 (+) TNF-α 在基质金属蛋白酶、MMP-2(72 kD 明胶酶 A)和 MMP-9(92 kD 明胶酶 B)的调节中的作用。人唾液腺细胞系 (HSG) 已被用作可能的体外模型来研究 IFN-γ + TNF-α 在 SS 发病机制中的作用。 HSG 细胞系在 IFN ± TNF-α 存在下,表现出 MMP-2 和 MMP-9 明胶分解活性、蛋白质和 RNA 水平增加。 MMP 活性的增加被抗 IFN-γ 受体的抗体部分阻断,这与之前描述的 IFN-γ ± TNF-α 抗增殖作用的完全抑制有关。然而,将 IFN-γ 处理的 HSG 细胞与合成 MMP 抑制剂 BB94 一起孵育并没有减轻这种抗增殖作用。此外,我们证明,与健康对照受试者相比,SS 患者唾液中的 MMP-9 水平非常高。这些数据表明细胞因子可以调节唾液上皮细胞产生 MMP,从而表明这些细胞在 SS 发病机制中的潜在作用。 J.细胞。生理学。 171:117–124, 1997。© 1997 Wiley-Liss, Inc.
Gelatinases have been shown to be regulated by many cytokines and growth factors, and have been implicated in the pathogenesis of certain autoimmune diseases via tissue destruction. High levels of several cytokines, including IFN‐γ and TNF‐α, have been demonstrated in the salivary gland microenvironment of patients with Sjo¨︁gren's syndrome (SS). How these cytokines may be contributing to the pathogenesis of this disease is not well understood. We hypothesized that IFN‐γ with or without (±) TNF‐α could be playing a role in the pathogenesis of SS via the regulation of matrix metalloproteinase (MMP) levels. This study examined the role of IFN‐γ and (+) TNF‐α in the regulation of the matrix metalloproteinases, MMP‐2 (72 kD gelatinase A) and MMP‐9 (92 kD gelatinase B). A human salivary gland cell line (HSG) has been used as a possible in vitro model to study the role of IFN‐γ + TNF‐α in the pathogenesis of SS. The HSG cell line, in the presence of IFN ± TNF‐α, displays increased MMP‐2 and MMP‐9 gelatinolytic activity, protein and RNA levels. The increase in MMP activity was partially blocked with an antibody against the IFN‐γ receptor, and this was associated with a complete inhibition of the previously described IFN‐γ ± TNF‐α antiproliferative effect. However, incubation of IFN‐γ treated HSG cells with the synthetic MMP inhibitor BB94 did not alleviate this antiproliferative effect. In addition, we demonstrate that there are very high levels of MMP‐9 in the saliva of patients with SS when compared to healthy control subjects. These data suggest that cytokines could be regulating MMP production by salivary epithelial cells and thus indicate a potential role for these cells in the pathogenesis of SS. J. Cell. Physiol. 171:117–124, 1997. © 1997 Wiley‐Liss, Inc.
干扰素-γ 协同上调培养的角质形成细胞中基质金属蛋白酶 (MMP)-1 和 MMP-3 的表达,但不上调金属蛋白酶组织抑制剂 (TIMP) 的表达。
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DOI: --
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