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Gene Review

IL32  -  interleukin 32

Homo sapiens

Synonyms: IL-32, IL-32alpha, IL-32beta, IL-32delta, IL-32gamma, ...
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Disease relevance of IL32


Psychiatry related information on IL32


High impact information on IL32


Chemical compound and disease context of IL32


Biological context of IL32


Anatomical context of IL32

  • Therefore, we evaluated the effects of adenoviral vector-mediated expression of NK4 on the biological behavior of a series of HCC cell lines in vitro and on HepG2 xenografts in vivo [1].
  • NK4 is an hepatocyte growth factor (HGF)-antagonist and a broad angiogenesis inhibitor [1].
  • RESULTS: We found that rvAdCMV/NK4 expression attenuated HGF-induced tumor cell scatter, migration, and basement membrane invasion (P<0.05), but did not inhibit tumor cell proliferation [2].
  • Moreover, after limited cleavage by PR3, IL-32alpha was more active than intact IL-32alpha in inducing macrophage inflammatory protein-2 in mouse macrophages and IL-8 in human peripheral blood mononuclear cells [10].
  • Here we show that chymases, which are chymotryptic peptidases secreted by mast cells, hydrolyze HGF, thereby abolishing scatter factor activity while generating an NK4-like antagonist of HGF scatter factor activity [15].

Associations of IL32 with chemical compounds


Physical interactions of IL32

  • HGF/NK4 competitively inhibited the specific binding of HGF to the receptor [22].

Regulatory relationships of IL32


Other interactions of IL32


Analytical, diagnostic and therapeutic context of IL32

  • NK4 gene therapy has confirmed antitumor efficacy on cancers with intact HGF-cMET signaling pathway [1].
  • Southern blot analysis of B lymphoblastoid lines derived from 18 unrelated individuals reveal variable banding patterns suggestive of polymorphism within the NK4 gene [16].
  • Our present findings further support the potential use of NK4 during radiotherapy for patients with pancreatic cancer [27].
  • The enhanced invasiveness of pancreatic cancer cells induced by coculture with irradiated fibroblasts was completely blocked by NK4, a specific antagonist of HGF [27].
  • Furthermore, systemic NK4 delivery by intraperitoneal injection of AdCMV.NK4 effectively suppressed both angiogenesis in the Matrigel assay (86% reduction, P<0.032), subcutaneous tumor growth in vivo (by 65% for H358, P<0.001), and hematogenous lung metastases without obvious side effects [28].


  1. Inhibition of angiogenesis and HGF-cMET-elicited malignant processes in human hepatocellular carcinoma cells using adenoviral vector-mediated NK4 gene therapy. Heideman, D.A., Overmeer, R.M., van Beusechem, V.W., Lamers, W.H., Hakvoort, T.B., Snijders, P.J., Craanen, M.E., Offerhaus, G.J., Meijer, C.J., Gerritsen, W.R. Cancer Gene Ther. (2005) [Pubmed]
  2. Effects of adenoviral-mediated gene transduction of NK4 on proliferation, movement, and invasion of human colonic LS174T cancer cells in vitro. Jie, J.Z., Wang, J.W., Qu, J.G., Wang, W., Hung, T. World J. Gastroenterol. (2006) [Pubmed]
  3. Inhibition of intracerebral glioblastoma growth by local treatment with the scatter factor/hepatocyte growth factor-antagonist NK4. Brockmann, M.A., Papadimitriou, A., Brandt, M., Fillbrandt, R., Westphal, M., Lamszus, K. Clin. Cancer Res. (2003) [Pubmed]
  4. Nk4, a new HGF/SF variant, is an antagonist to the influence of HGF/SF on the motility and invasion of colon cancer cells. Parr, C., Hiscox, S., Nakamura, T., Matsumoto, K., Jiang, W.G. Int. J. Cancer (2000) [Pubmed]
  5. Rheumatoid arthritis and interleukin-32. Shoda, H., Fujio, K., Yamamoto, K. Cell. Mol. Life Sci. (2007) [Pubmed]
  6. Interleukin-32 expression in the pancreas. Nishida, A., Andoh, A., Inatomi, O., Fujiyama, Y. J. Biol. Chem. (2009) [Pubmed]
  7. The frequency of visual hallucinations in schizophrenic patients in Saudi Arabia. Zarroug, E.T. The British journal of psychiatry : the journal of mental science. (1975) [Pubmed]
  8. Complications of combined antiepileptic therapy. Sawas, A.H., Sultan, A.M., Amasha, M.H. East African medical journal. (1992) [Pubmed]
  9. Interleukin-32: a cytokine and inducer of TNFalpha. Kim, S.H., Han, S.Y., Azam, T., Yoon, D.Y., Dinarello, C.A. Immunity (2005) [Pubmed]
  10. Proteinase 3 is an IL-32 binding protein. Novick, D., Rubinstein, M., Azam, T., Rabinkov, A., Dinarello, C.A., Kim, S.H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. IL-32, a proinflammatory cytokine in rheumatoid arthritis. Joosten, L.A., Netea, M.G., Kim, S.H., Yoon, D.Y., Oppers-Walgreen, B., Radstake, T.R., Barrera, P., van de Loo, F.A., Dinarello, C.A., van den Berg, W.B. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  12. Preclinical study of a "tailor-made" combination of NK4-expressing gene therapy and gefitinib (ZD1839, Iressatrade mark) for disseminated peritoneal scirrhous gastric cancer. Namiki, Y., Namiki, T., Yoshida, H., Date, M., Yashiro, M., Matsumoto, K., Nakamura, T., Yanagihara, K., Tada, N., Satoi, J., Fujise, K. Int. J. Cancer (2006) [Pubmed]
  13. Adenoviral-mediated gene transduction of the hepatocyte growth factor (HGF) antagonist, NK4, suppresses peritoneal metastases of gastric cancer in nude mice. Ueda, K., Iwahashi, M., Matsuura, I., Nakamori, M., Nakamura, M., Ojima, T., Naka, T., Ishida, K., Matsumoto, K., Nakamura, T., Yamaue, H. Eur. J. Cancer (2004) [Pubmed]
  14. Peritumoral injection of adenovirus vector expressing NK4 combined with gemcitabine treatment suppresses growth and metastasis of human pancreatic cancer cells implanted orthotopically in nude mice and prolongs survival. Ogura, Y., Mizumoto, K., Nagai, E., Murakami, M., Inadome, N., Saimura, M., Matsumoto, K., Nakamura, T., Maemondo, M., Nukiwa, T., Tanaka, M. Cancer Gene Ther. (2006) [Pubmed]
  15. Mast cell and neutrophil peptidases attack an inactivation segment in hepatocyte growth factor to generate NK4-like antagonists. Raymond, W.W., Cruz, A.C., Caughey, G.H. J. Biol. Chem. (2006) [Pubmed]
  16. Identification of a novel gene expressed in activated natural killer cells and T cells. Dahl, C.A., Schall, R.P., He, H.L., Cairns, J.S. J. Immunol. (1992) [Pubmed]
  17. Suppression of the progress of disseminated pancreatic cancer cells by NK4 plasmid DNA released from cationized gelatin microspheres. Kushibiki, T., Matsumoto, K., Nakamura, T., Tabata, Y. Pharm. Res. (2004) [Pubmed]
  18. Enhanced suppression of tumor growth using a combination of NK4 plasmid DNA-PEG engrafted cationized dextran complex and ultrasound irradiation. Hosseinkhani, H., Kushibiki, T., Matsumoto, K., Nakamura, T., Tabata, Y. Cancer Gene Ther. (2006) [Pubmed]
  19. Hepatic gene expression of NK4, an HGF-antagonist/angiogenesis inhibitor, suppresses liver metastasis and invasive growth of colon cancer in mice. Wen, J., Matsumoto, K., Taniura, N., Tomioka, D., Nakamura, T. Cancer Gene Ther. (2004) [Pubmed]
  20. IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1beta and IL-6 production through a caspase 1-dependent mechanism. Netea, M.G., Azam, T., Ferwerda, G., Girardin, S.E., Walsh, M., Park, J.S., Abraham, E., Kim, J.M., Yoon, D.Y., Dinarello, C.A., Kim, S.H. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  21. Tumor necrosis factor alpha-induced interleukin-32 is positively regulated via the Syk/protein kinase Cdelta/JNK pathway in rheumatoid synovial fibroblasts. Mun, S.H., Kim, J.W., Nah, S.S., Ko, N.Y., Lee, J.H., Kim, J.D., Kim, D.K., Kim, H.S., Choi, J.D., Kim, S.H., Lee, C.K., Park, S.H., Kim, B.K., Kim, H.S., Kim, Y.M., Choi, W.S. Arthritis Rheum. (2009) [Pubmed]
  22. HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor. Date, K., Matsumoto, K., Shimura, H., Tanaka, M., Nakamura, T. FEBS Lett. (1997) [Pubmed]
  23. HGF/NK4 inhibited VEGF-induced angiogenesis in in vitro cultured endothelial cells and in vivo rabbit model. Nakabayashi, M., Morishita, R., Nakagami, H., Kuba, K., Matsumoto, K., Nakamura, T., Tano, Y., Kaneda, Y. Diabetologia (2003) [Pubmed]
  24. Antagonistic effect of NK4 on HGF/SF induced changes in the transendothelial resistance (TER) and paracellular permeability of human vascular endothelial cells. Martin, T.A., Mansel, R.E., Jiang, W.G. J. Cell. Physiol. (2002) [Pubmed]
  25. Antagonistic effect of NK4, a novel hepatocyte growth factor variant, on in vitro angiogenesis of human vascular endothelial cells. Jiang, W.G., Hiscox, S.E., Parr, C., Martin, T.A., Matsumoto, K., Nakamura, T., Mansel, R.E. Clin. Cancer Res. (1999) [Pubmed]
  26. Tumor suppression through angiogenesis inhibition by SUIT-2 pancreatic cancer cells genetically engineered to secrete NK4. Saimura, M., Nagai, E., Mizumoto, K., Maehara, N., Minamishima, Y.A., Katano, M., Matsumoto, K., Nakamura, T., Tanaka, M. Clin. Cancer Res. (2002) [Pubmed]
  27. Radiation to stromal fibroblasts increases invasiveness of pancreatic cancer cells through tumor-stromal interactions. Ohuchida, K., Mizumoto, K., Murakami, M., Qian, L.W., Sato, N., Nagai, E., Matsumoto, K., Nakamura, T., Tanaka, M. Cancer Res. (2004) [Pubmed]
  28. Targeting angiogenesis and HGF function using an adenoviral vector expressing the HGF antagonist NK4 for cancer therapy. Maemondo, M., Narumi, K., Saijo, Y., Usui, K., Tahara, M., Tazawa, R., Hagiwara, K., Matsumoto, K., Nakamura, T., Nukiwa, T. Mol. Ther. (2002) [Pubmed]
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