Noma Naruto, Asagiri Masataka, Takeiri Masatoshi, Ohmae Saori, Takemoto Kenji, Iwaisako Keiko, Minato Nagahiro, Maeda-Yamamoto Mari, Simizu Siro, Umezawa Kazuo
Innovation Center for Immunoregulation and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Int Arch Allergy Immunol. 2015;166(2):84-90. doi: 10.1159/000371419. Epub 2015 Mar 13.
Stimulation with antigen and IgE is known to activate NF-κB in mast cells. In the present research, we studied the role of NF-κB on cellular migration in mast cell-like RBL-2H3 cells and bone marrow-derived mast cells (BMMCs) using the NF-κB inhibitor (-)-DHMEQ.
A Matrigel invasion chamber was used to evaluate cell migration. A PCR array was used to screen the expression of 84 key genes involved in cell migration.
(-)-DHMEQ inhibited antigen/IgE-induced NF-κB activation and expressions of its target genes such as IL-6 and TNF-α. (-)-DHMEQ was found to inhibit in vitro invasion toward the antigen without any toxicity. We then looked for NF-κB-dependent genes that would be important for mast cell invasion using the PCR array. (-)-DHMEQ was found to lower the expression of matrix metalloproteinase (MMP)-2. The MMP inhibitor GM6001 also inhibited cellular invasion toward the antigen. These effects of (-)-DHMEQ were obtained in both RBL-2H3 cells and BMMCs.
These findings indicate that (-)-DHMEQ suppressed mast cell migration via the inhibition of NF-κB-regulated MMP-2 expression.
已知抗原和IgE刺激可激活肥大细胞中的核因子κB（NF-κB）。在本研究中，我们使用NF-κB抑制剂（-）-DHMEQ研究了NF-κB在类肥大细胞RBL-2H3细胞和骨髓来源的肥大细胞（BMMCs）细胞迁移中的作用。
使用基质胶侵袭小室评估细胞迁移。使用PCR阵列筛选84个参与细胞迁移的关键基因的表达。
（-）-DHMEQ抑制抗原/IgE诱导的NF-κB激活及其靶基因如IL-6和TNF-α的表达。发现（-）-DHMEQ可抑制体外对抗原的侵袭且无任何毒性。然后我们使用PCR阵列寻找对肥大细胞侵袭重要的NF-κB依赖性基因。发现（-）-DHMEQ可降低基质金属蛋白酶（MMP）-2的表达。MMP抑制剂GM6001也抑制细胞对抗原的侵袭。（-）-DHMEQ的这些作用在RBL-2H3细胞和BMMCs中均有体现。
这些发现表明（-）-DHMEQ通过抑制NF-κB调节的MMP-2表达来抑制肥大细胞迁移。
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