Recombinant Human IL-32 gamma Protein, CF

Interleukin-32 gamma (IL-32 gamma), a proinflammatory cytokine previously termed natural killer cells transcript 4 (NK4) (also tumor necrosis factor alpha (TNF alpha) -inducing factor), is a 27 kDa, secreted glycoprotein that belongs to no known cytokine family (1). Little is known about it. However, because it has the ability to induce proinflammatory cytokines such as TNF alpha and IL-8 in THP-1 cells, and activates typical cytokine signaling pathways involving NF-kappa B and p38, IL-32 is considered to be a cytokine (2). Human IL-32 gamma is 234 amino acids (aa) in length (1). It contains a 30 aa signal sequence, plus a 204 aa mature region that possesses three potential myristoylation sites and one potential N-linked glycosylation site (1, 2). IL-32 gamma represents the standard protein, and is the first isoform. In addition, there are five potential alternate splice forms (3). IL-32 alpha lacks two of the splicing variant regions found in IL-32 gamma (aa 19 - 64 and aa 154 - 210). IL-32 beta is missing aa 19 - 64, and IL-32 delta is missing aa 1 - 10 and aa 19 - 64. IL-32 epsilon and IL-32 zeta are novel isoforms that have not yet been characterized. Human IL-32 gamma is active in mouse cells (2). No rodent orthologs have been reported. No putative IL-32 receptor has been found, but using the isoform IL-32 alpha, the protein proved to bind to proteinase 3 (PR3) (4, 5). IL-32 is involved in activation-induced cell death in T cells (3) and is highly expressed in tissues in a number of disease states including the synovial tissue in rheumatoid arthritis (5, 6) and human colon epithelial tissue in Crohn’s disease (5). Using siRNA to endogenous IL-32 in primary human blood monocytes, there were significant decreases (greater than 50%) in IFN-gamma, TNF, and IL-6, suggesting that endogenous IL-32 is upstream in the cytokine cascade in monocytes (7). Increased levels of IL-32 during human immunodeficiency virus (HIV) infection may play a protective role by suppressing HIV replication (8). In addition, mycobacteria species are potent stimuli for the production of IL-32 from human monocytes and macrophages (9).