Identification of the most active interleukin-32 isoform

被引:164
作者
Choi, Ji-Da [1 ]
Bae, Su-Young [1 ]
Hong, Jae-Woo [1 ]
Azam, Tania [2 ]
Dinarello, Charles A. [2 ]
Her, Erk [3 ]
Choi, Whan-Soo [3 ]
Kim, Bo-Kyung [4 ]
Lee, Chang-Kwon [4 ]
Yoon, Do-Young [5 ]
Kim, Sun-Jong [6 ]
Kim, Soo-Hyun [1 ]
机构
[1] Konkuk Univ, Inst Biomed Sci & Technol, Coll Med, Lab Cytokine Immunol, Seoul 143701, South Korea
[2] Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO USA
[3] Konkuk Univ, Coll Med, Dept Immunol, Chungju City, Chungbuk, South Korea
[4] Konkuk Univ, Coll Med, Dept Physiol, Chungju City, Chungbuk, South Korea
[5] Konkuk Univ, Coll Med, Dept Biosci & Biotechnol, Seoul, South Korea
[6] Konkuk Univ, Coll Med, Dept Resp Med, Seoul, South Korea
基金
美国国家卫生研究院;
关键词
autoimmunity; cytokine; endotoxin; lipopolysaccharide; inflammation; innate immunity; TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; CROHNS-DISEASE; BIOLOGICAL-ACTIVITY; THERAPEUTIC TARGET; BINDING-PROTEIN; IL-32; SUSCEPTIBILITY; RECEPTOR; IL-18;
D O I
10.1111/j.1365-2567.2008.02917.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Cytokines are crucial in host defence against pathogens such as bacteria, viruses, fungi and parasites. A newly described cytokine, interleukin-32 (IL-32), induces various proinflammatory cytokines (tumour necrosis factor-alpha, IL-1 beta, IL-6) and chemokines in both human and mouse cells through the nuclear factor-kappa B and p38 mitogen-activated protein kinase inflammatory signal pathway. The IL-32 primarily acts on monocytic cells rather than T cells. In an attempt to isolate the IL-32 soluble receptor, we used an IL-32 ligand-affinity column to purify neutrophil proteinase 3, which is a serine proteinase involved in many inflammatory diseases. IL-32 has biological activity associated with Mycobacterium tuberculosis and chronic proinflammatory diseases such as rheumatoid arthritis. IL-32 is transcribed as six alternative splice variants and the biological activity of each individual isoform remains unknown. Here, we cloned the complementary DNA of the four IL-32 isoforms (alpha, beta, gamma and delta) that are the most representative IL-32 transcripts. To produce recombinant protein with a high yield, the amino acids of two cysteine residues were mutated to serine residues, because serine residues are not conserved among different species. The multi-step purified recombinant IL-32 isoform proteins were assessed for their biological activities with different cytokine assays. The gamma isoform of IL-32 was the most active, although all isoforms were biologically active. The present study will provide a specific target to neutralize endogenous IL-32, which may contribute to basic and clinical immunology.
引用
收藏
页码:535 / 542
页数:8
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