Involvement of caspase-1 and caspase-3 in the production and processing of mature human interleukin 18 in monocytic THP.1 cells

被引：198

作者：

Akita, K ^{[1
]}

Ohtsuki, T ^{[1
]}

Nukada, Y ^{[1
]}

Tanimoto, T ^{[1
]}

Namba, M ^{[1
]}

Okura, T ^{[1
]}

TakakuraYamamoto, R ^{[1
]}

Torigoe, K ^{[1
]}

Gu, Y ^{[1
]}

Su, MSS ^{[1
]}

Fujii, M ^{[1
]}

SatohItoh, M ^{[1
]}

Yamamoto, K ^{[1
]}

Kohno, K ^{[1
]}

Ikeda, M ^{[1
]}

Kurimoto, M ^{[1
]}

机构：

[1] VERTEX PHARMACEUT INC,CAMBRIDGE,MA 02139

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 1997年 / 272卷 / 42期

关键词：

D O I：

10.1074/jbc.272.42.26595

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Recently, human interleukin 18 (hIL-18) cDNA was cloned, and the recombinant protein with a tentatively assigned NH2-terminal amino acid sequence was generated. However, natural hIL-18 has not yet been isolated, and its cellular processing is therefore still unclear. To clarify this, we purified natural hIL-18 from the cytosolic extract of monocytic THP.1 cells. Natural hIL-18 exhibited a molecular mass of 18.2 kDa, and the NH2-terminal amino acid was Tyr(37). Biological activities of the purified protein were identical to those of recombinant hIL-18 with respect to the enhancement of natural killer cell cytotoxicity and interferon-gamma production by human peripheral blood mononuclear cells. We also found two precursor hIL-18 (prohIL-18)-processing activities in the cytosol of THP.1 cells, These activities were blocked separately by the caspase inhibitors Ac-YVAD-CHO and Ac-DEVD-CHO. Further analyses of the partially purified enzymes revealed that one is caspase-1, which cleaves prohIL-18 at the Asp(36)-Tyr(37) Site to generate the mature hIL-18, and the other is caspase-3, which cleaves both precursor and mature hIL-18 at Asp(71)-Ser(72) and Asp(76)-Asn(77) to generate biologically inactive products, These results suggest that the production and processing of natural hIL-18 are regulated by two processing enzymes, caspase-1 and caspase-3, in THP.1 cells.

引用

页码：26595 / 26603

页数：9

共 36 条

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