Interleukin-32: a cytokine and inducer of TNFalpha.
We describe the gene structure, regulation, signal transduction. and functions of a cytokine, interleukin (IL)-32. An IL-18 unresponsive cell was converted to a responsive cell by transfection of the IL-18 receptor beta chain, and IL-18-induced microarray revealed high expression of a cytokine-like gene. Although IL-32 does not share sequence homology with known cytokine families, IL-32 induces various cytokines, human TNFalpha, and IL-8 in THP-1 monocytic cells as well as mouse TNFalpha and MIP-2 in Raw macrophage cells. IL-32 activates typical cytokine signal pathways of nuclear factor-kappa B (NF-kappaB) and p38 mitogen-activated protein kinase. IL-32 mRNA is highly expressed in immune tissue rather than other tissues. Human IL-32 exists as four splice variants, and IL-32 from other species were found as expressed sequence tag clones in the databank. Induced in human peripheral lymphocyte cells after mitogen stimulation, in human epithelial cells by IFNgamma, and in NK cells after exposure to the combination of IL-12 plus IL-18, IL-32 may play a role in inflammatory/autoimmune diseases.
Kim
Soo-Hyun
SH
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. soohyun.kim@uchsc.edu
Han
Sun-Young
SY
Azam
Tania
T
Yoon
Do-Young
DY
Dinarello
Charles A
CA
D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016207:Cytokines; C496971:IL32 protein, human; D020382:Interleukin-18; D007378:Interleukins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C569037:interleukin-32, mouse