Identification of the most active interleukin-32 isoform

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-α, IL-1β, IL-6) and chemokines in both human and mouse cells through the nucle...

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Bibliographic Details
Published in:Immunology 2009-04, Vol.126 (4), p.535-542
Main Authors: Choi, Ji-Da, Bae, Su-Young, Hong, Jae-Woo, Azam, Tania, Dinarello, Charles A, Her, Erk, Choi, Whan-Soo, Kim, Bo-Kyung, Lee, Chang-Kwon, Yoon, Do-Young, Kim, Sun-Jong, Kim, Soo-Hyun
Format: Article
Language:English
Subjects:
Animals
autoimmunity
Biological Assay - methods
Cells, Cultured
Cysteine - genetics
cytokine
Cytokines - biosynthesis
endotoxin/lipopolysaccharide
Epithelial Cells - immunology
Gene Expression Regulation - immunology
Humans
immunity
inflammation
innate immunity
Interleukins - biosynthesis
Interleukins - genetics
Interleukins - immunology
Macrophages, Peritoneal - immunology
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mutation
Mycobacterium tuberculosis
Original
Protein Isoforms - biosynthesis
Protein Isoforms - genetics
Protein Isoforms - immunology
Recombinant Proteins - biosynthesis
Reverse Transcriptase Polymerase Chain Reaction - methods
RNA, Messenger - genetics
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Summary: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-α, IL-1β, IL-6) and chemokines in both human and mouse cells through the nuclear factor-κB 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 (α, β, γ and δ) 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 γ 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.
ISSN:0019-2805
1365-2567
DOI:10.1111/j.1365-2567.2008.02917.x