Interleukin-1F7B (IL-1H4/IL-1F7) is processed by caspase-1 and mature IL-1F7B binds to the IL-18 receptor but does not induce IFN-γ production
Interleukin-1F7B (IL-1H4/IL-1F7) is processed by caspase-1 and mature IL-1F7B binds to the IL-18 receptor but does not induce IFN-γ production
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DOI：
10.1006/cyto.2002.0873
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发表时间：
2002-04-21
期刊：
影响因子：
3.8
通讯作者：
Lotze, MT
中科院分区：
文献类型：
--
作者：
Kumar, S;Hanning, CR;Lotze, MT
我们最近报道了四个新的白细胞介素-1（IL-1）家族成员的鉴定，我们将其命名为IL-1同系物1-4（IL-1H 1 -4）。这些蛋白质与IL-1家族的其他成员具有显著的序列同源性。在这些同源物中，只有IL-1H 4（重命名为IL-IF 7 b）被预测含有前肽结构域和半胱天冬酶切割位点。我们现在报道半胱天冬酶-1在预测的位点切割IL-1F 7 b以产生成熟的IL-1F 7 b。胱天蛋白酶-4也能够处理IL-IF 7 b，尽管效率低下。其它半胱天冬酶和颗粒酶-B不切割IL-IF 7 b。此外，腺病毒介导的HEK 293细胞中IL-IF 7 b的表达导致成熟IL-IF 7 b的原位加工和分泌。在鉴定潜在受体的筛选中，原IL-IF 7 b和成熟IL-IF 7 b均与可溶性IL-18受体α-Fc（IL-18 α-Fc）结合，但不与可溶性IL-1 R-Fc或ST 2 R-Fc融合蛋白结合。成熟的IL-1F 7 b以比前体形式更高的亲和力结合IL-18 Ra-Fc蛋白，尽管对两种蛋白的亲和力显著低于对IL-18观察到的亲和力。与该观察结果一致，仅IL-18而非IL-1F 7 b诱导KG 1a细胞产生IFN-γ。我们还报告了亲和成熟的IL-IF 7 b形成同源二聚体，其缔合常数分别为4 μ M和5 nM，表明与1 L-1F 7 b加工的生物学相关性。最后，我们已经定位了IL-IF 7 b蛋白在离散细胞群中的表达，包括浆细胞和肿瘤细胞。这些数据表明IL-IF 7 b可能参与免疫应答、炎性疾病和/或癌症。(C)2002爱思唯尔科技有限公司版权所有。
We have recently reported the identification of four novel members of the interleukin-1 (IL-1) family which we designated as IL-1 homologue 1-4 (IL-1H1-4). These proteins exhibit significant sequence homology to other members of the IL-1 family. Of these homologues, only IL-1H4 (renamed IL-IF7b) was predicted to contain a propeptide domain and a caspase cleavage site. We now report that caspase-1 cleaves IL-IF7b at the predicted site to generate mature IL-IF7b. Caspase-4 was also able to process IL-IF7b, albeit inefficiently. Other caspases and Granzyme-B did not cleave IL-IF7b. Furthermore, adenovirus-mediated expression of IL-IF7b in HEK 293 cells led to in situ processing and secretion of mature IL-IF7b. In a screen to identify a potential receptor, both pro and mature IL-IF7b bound to the soluble IL-18 receptor alpha-Fc (IL-18Ralpha-Fc) but not to the soluble IL-1R-Fc or ST2R-Fc fusion proteins. Mature 1L-1F7b bound to the IL-18Ra-Fc protein with higher affinity than the pro form, although the affinities for both proteins were significantly lower than that observed for IL-18. Consistent with this observation, only IL-18 and not lL-1F7b induced IFN-gamma production by KG1a cells. We also report that pro and mature IL-IF7b form homodimers with association constants of 4 muM and 5 nM, respectively, suggesting biological relevance to 1L-1F7b processing. Finally, we have localized the expression of IL-IF7b protein in discrete cell populations including plasma cells and tumor cells. These data suggest that IL-IF7b may be involved in immune response, inflammatory diseases and/or cancer. (C) 2002 Elsevier Science Ltd. All rights reserved.