Suzuki Motohiko, Itoh Makoto, Ohta Nobuo, Nakamura Yoshihisa, Moriyama Akihiko, Matsumoto Tamami, Ohashi Taku, Murakami Shingo
Department of Otorhinolaryngology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
Acta Otolaryngol. 2006 Jul;126(7):746-51. doi: 10.1080/00016480500475625.
Allergic responses specific to the corresponding proteases were reduced by protease inhibitors, suggesting promise as potent treatments for allergic rhinitis and other allergic conditions.
Allergic diseases, such as allergic rhinitis, are caused by the overproduction of IgE antibodies to various allergens. Many reported allergens are proteases that are cysteine, serine, aspartic (acid) proteases and metalloproteases. Conjugation of E64 inhibitor with cysteine protease allergens inhibits the IgE response to the same allergens. However, whether inhibitors of the other protease families reduce IgE levels and whether protease inhibitors reduce allergic symptoms remain controversial. Therefore, we compared the abilities of active and inhibitor-blocked inactive forms of proteases to generate IgE and allergic symptoms in this study to evaluate associations between the allergic response and protease inhibitors.
We measured levels of IgE, IgG1, IgG2a, and IgG2b enzyme-specific antibodies, and counted frequency of sneezing and nasal rubbing behavior in mice immunized with active or inactive forms of bromelain, chymotrypsin, chymosin and collagenase (a cysteine protease, a serine protease, an aspartic protease and a metalloprotease, respectively).
All the inhibitors reduced IgE and IgG1 production in response to corresponding enzymes, and a cysteine protease inhibitor, E64, decreased nasal symptoms, such as sneezing and nasal rubbing.
蛋白酶抑制剂可降低对相应蛋白酶的过敏反应,这表明其有望成为治疗过敏性鼻炎和其他过敏病症的有效疗法。
过敏性疾病,如过敏性鼻炎,是由针对各种过敏原的IgE抗体过度产生所致。许多已报道的过敏原是蛋白酶,包括半胱氨酸蛋白酶、丝氨酸蛋白酶、天冬氨酸蛋白酶和金属蛋白酶。E64抑制剂与半胱氨酸蛋白酶过敏原结合可抑制对相同过敏原的IgE反应。然而,其他蛋白酶家族的抑制剂是否能降低IgE水平以及蛋白酶抑制剂是否能减轻过敏症状仍存在争议。因此,在本研究中,我们比较了蛋白酶的活性形式和抑制剂阻断的无活性形式产生IgE和过敏症状的能力,以评估过敏反应与蛋白酶抑制剂之间的关联。
我们测量了用菠萝蛋白酶、胰凝乳蛋白酶、凝乳酶和胶原酶(分别为半胱氨酸蛋白酶、丝氨酸蛋白酶、天冬氨酸蛋白酶和金属蛋白酶)的活性或无活性形式免疫的小鼠中IgE、IgG1、IgG2a和IgG2b酶特异性抗体的水平,并统计了打喷嚏和擦鼻行为的频率。
所有抑制剂均降低了对相应酶的IgE和IgG1产生,一种半胱氨酸蛋白酶抑制剂E64减轻了打喷嚏和擦鼻等鼻部症状。