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Gene Review

GNLY  -  granulysin

Homo sapiens

Synonyms: 519, D2S69E, Granulysin, LAG-2, LAG2, ...
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Disease relevance of GNLY

  • In vivo effects of GNLY were evaluated using the syngeneic T lymphoma tumor C6VL [1].
  • Granulysin (GNLY) is a cytolytic molecule expressed by human CTL and NK cells with activity against a variety of tumors and microbes, including Mycobacterium tuberculosis [1].
  • We propose that CD8(+)CD57(+) cells were Ag-driven effector cells with very high cytotoxic effector potential including perforin, granzymes, and granulysin, regardless of HIV status [2].
  • Uptake of granulysin via lipid rafts leads to lysis of intracellular Listeria innocua [3].
  • Pertussis toxin treatment abrogates chemoattraction by granulysin, indicating involvement of G-protein-coupled receptor(s) [4].

Psychiatry related information on GNLY

  • We developed a novel vaccine formulation by incorporating Id protein with liposomal lymphokine that was more potent than a prototype, carrier-conjugated Id protein vaccine in preclinical studies [5].
  • We have previously shown that this marker is profusely expressed in cortex of elderly and Alzheimer's disease (AD) patients, as is the receptor for the lymphokine interleukin-2 [6].
  • Lifestyles and mental health status are associated with natural killer cell and lymphokine-activated killer cell activities [7].

High impact information on GNLY


Chemical compound and disease context of GNLY


Biological context of GNLY


Anatomical context of GNLY

  • Following stimulation by the C. neoformans mitogen, CD8 T cells expressed granulysin and acquired antifungal activity [17].
  • Allospecific cell lines generated from GNLY transgenic animals showed enhanced killing of target cells [1].
  • GNLY mRNA is highest in spleen, with detectable expression in thymus and lungs, and minimal expression in heart, kidney, liver, muscle, intestine, and brain [1].
  • Human tumor cell line resistance to chemotherapeutic agents does not predict resistance to natural killer or lymphokine-activated killer cell-mediated cytolysis [19].
  • Lymphocyte activation was determined by measurement of proliferative responses and lymphokine release [20].

Associations of GNLY with chemical compounds

  • Concanamycin A and EGTA did not affect the antifungal effect, suggesting that the activity of granulysin was perforin independent [17].
  • Unlike 519, the predicted NKG5 polypeptide has an NH2-terminal sequence that is strongly hydrophobic, characteristic of a signal peptide, and lacks any additional hydrophobic regions in the remainder of the peptide, suggesting that NKG5 encodes a secreted protein [21].
  • In contrast to previous findings in mice, the arginine analogue, NG-monomethyl-L-arginine, significantly inhibited both proliferation and lymphokine release by superantigen-stimulated human cells [20].
  • Thus, our results demonstrate that pyocyanine inhibits T cell proliferation by decreasing the production of the critical lymphokine IL 2 and by decreasing the expression of the IL 2 receptor [22].
  • RESULTS: Granulysin mRNA increase (vs. 95% confidence interval of 159 urine samples from nonrejecting patients) was detected during 11 of 14 aRx episodes, and follow-up studies showed its predictive value for delayed aRx episodes, even weeks before enhanced serum creatinine was observed [23].

Physical interactions of GNLY


Regulatory relationships of GNLY


Other interactions of GNLY

  • In addition to classic MDR, RV+ cells displayed relative resistance to complement-mediated cytotoxicity with both immunoglobulin G and M antibodies against different cell surface antigens, but not to antibody-dependent cellular cytotoxicity and lymphokine-activated killing [28].
  • Furthermore, IL-15 was both necessary and sufficient for granulysin up-regulation in CD8 T cells [17].
  • CONCLUSIONS: We demonstrate the upregulation of immune-related genes IL-15Ralpha, Lpn and NKG5 in secretory versus proliferative human endometrium [29].
  • These experiments demonstrate the production of a human lymphocyte factor (lymphokine) that induces LP synthesis [30].
  • The 9-kDa product is a processed form of 519 and differs from the 15-kDa product in both its amino and carboxyl terminus [31].

Analytical, diagnostic and therapeutic context of GNLY


  1. Granulysin-mediated tumor rejection in transgenic mice. Huang, L.P., Lyu, S.C., Clayberger, C., Krensky, A.M. J. Immunol. (2007) [Pubmed]
  2. High Cytotoxic and Specific Migratory Potencies of Senescent CD8+CD57+ Cells in HIV-Infected and Uninfected Individuals. Le Priol, Y., Puthier, D., L??cureuil, C., Combadi??re, C., Debr??, P., Nguyen, C., Combadi??re, B. J. Immunol. (2006) [Pubmed]
  3. Uptake of granulysin via lipid rafts leads to lysis of intracellular Listeria innocua. Walch, M., Eppler, E., Dumrese, C., Barman, H., Groscurth, P., Ziegler, U. J. Immunol. (2005) [Pubmed]
  4. Granulysin, a cytolytic molecule, is also a chemoattractant and proinflammatory activator. Deng, A., Chen, S., Li, Q., Lyu, S.C., Clayberger, C., Krensky, A.M. J. Immunol. (2005) [Pubmed]
  5. Human autologous tumor-specific T-cell responses induced by liposomal delivery of a lymphoma antigen. Neelapu, S.S., Baskar, S., Gause, B.L., Kobrin, C.B., Watson, T.M., Frye, A.R., Pennington, R., Harvey, L., Jaffe, E.S., Robb, R.J., Popescu, M.C., Kwak, L.W. Clin. Cancer Res. (2004) [Pubmed]
  6. Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer's disease. Rogers, J., Luber-Narod, J., Styren, S.D., Civin, W.H. Neurobiol. Aging (1988) [Pubmed]
  7. Lifestyles and mental health status are associated with natural killer cell and lymphokine-activated killer cell activities. Morimoto, K., Takeshita, T., Inoue-Sakurai, C., Maruyama, S. Sci. Total Environ. (2001) [Pubmed]
  8. Potassium and calcium channels in lymphocytes. Lewis, R.S., Cahalan, M.D. Annu. Rev. Immunol. (1995) [Pubmed]
  9. Lymphokine production by human T cells in disease states. Romagnani, S. Annu. Rev. Immunol. (1994) [Pubmed]
  10. Signal transduction by lymphocyte antigen receptors. Weiss, A., Littman, D.R. Cell (1994) [Pubmed]
  11. Regulation of genes for HLA class II antigens in cell lines from patients with severe combined immunodeficiency. de Préval, C., Hadam, M.R., Mach, B. N. Engl. J. Med. (1988) [Pubmed]
  12. Combined effect of epirubicin and lymphokine-activated killer cells on the resistant human breast cancer cells. Ozkan, A., Ayhan, A., Fiskin, K. Cell Biol. Toxicol. (2004) [Pubmed]
  13. Ontogeny of Fc receptors and complement receptor (CR3) during human myeloid differentiation. Fleit, H.B., Wright, S.D., Durie, C.J., Valinsky, J.E., Unkeless, J.C. J. Clin. Invest. (1984) [Pubmed]
  14. Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of human macrophages without impairing their responsiveness to gamma interferon. Schaffner, A. J. Clin. Invest. (1985) [Pubmed]
  15. Fibronectin and alpha5 integrin regulate keratinocyte cell cycling. A mechanism for increased fibronectin potentiation of T cell lymphokine-driven keratinocyte hyperproliferation in psoriasis. Bata-Csorgo, Z., Cooper, K.D., Ting, K.M., Voorhees, J.J., Hammerberg, C. J. Clin. Invest. (1998) [Pubmed]
  16. Soluble antigen abrogates the appearance of anti-protein IgG1-forming cell precursors during primary immunization. Nossal, G.J., Karvelas, M. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  17. CD8 T cell-mediated killing of Cryptococcus neoformans requires granulysin and is dependent on CD4 T cells and IL-15. Ma, L.L., Spurrell, J.C., Wang, J.F., Neely, G.G., Epelman, S., Krensky, A.M., Mody, C.H. J. Immunol. (2002) [Pubmed]
  18. The isolation and sequence of a novel gene from a human functional T cell line. Jongstra, J., Schall, T.J., Dyer, B.J., Clayberger, C., Jorgensen, J., Davis, M.M., Krensky, A.M. J. Exp. Med. (1987) [Pubmed]
  19. Human tumor cell line resistance to chemotherapeutic agents does not predict resistance to natural killer or lymphokine-activated killer cell-mediated cytolysis. Harker, W.G., Tom, C., McGregor, J.R., Slade, L., Samlowski, W.E. Cancer Res. (1990) [Pubmed]
  20. Bacterial superantigen-induced human lymphocyte responses are nitric oxide dependent and mediated by IL-12 and IFN-gamma. Sriskandan, S., Evans, T.J., Cohen, J. J. Immunol. (1996) [Pubmed]
  21. A cDNA clone expressed in natural killer and T cells that likely encodes a secreted protein. Yabe, T., McSherry, C., Bach, F.H., Houchins, J.P. J. Exp. Med. (1990) [Pubmed]
  22. Studies on the mechanism of T cell inhibition by the Pseudomonas aeruginosa phenazine pigment pyocyanine. Nutman, J., Berger, M., Chase, P.A., Dearborn, D.G., Miller, K.M., Waller, R.L., Sorensen, R.U. J. Immunol. (1987) [Pubmed]
  23. Enhanced granulysin mRNA expression in urinary sediment in early and delayed acute renal allograft rejection. Kotsch, K., Mashreghi, M.F., Bold, G., Tretow, P., Beyer, J., Matz, M., Hoerstrup, J., Pratschke, J., Ding, R., Suthanthiran, M., Volk, H.D., Reinke, P. Transplantation (2004) [Pubmed]
  24. Opposing roles of activator protein-1 and CCAAT/enhancer binding protein beta in the regulation of inducible granulysin gene expression in a human monocytic cell line, THP-1. Kida, Y., Shimizu, T., Kuwano, K. Immunology (2002) [Pubmed]
  25. Lymphokine-activated killer cell susceptibility and multidrug resistance in small cell lung carcinoma. Savas, B., Kerr, P.E., Ustun, H., Cole, S.P., Pross, H.F. Anticancer Res. (1998) [Pubmed]
  26. Leukoregulin induces plasminogen activator inhibitor type 1 in human orbital fibroblasts. Hogg, M.G., Evans, C.H., Smith, T.J. Am. J. Physiol. (1995) [Pubmed]
  27. A distinct pathway of cell-mediated apoptosis initiated by granulysin. Kaspar, A.A., Okada, S., Kumar, J., Poulain, F.R., Drouvalakis, K.A., Kelekar, A., Hanson, D.A., Kluck, R.M., Hitoshi, Y., Johnson, D.E., Froelich, C.J., Thompson, C.B., Newmeyer, D.D., Anel, A., Clayberger, C., Krensky, A.M. J. Immunol. (2001) [Pubmed]
  28. The multidrug resistance phenotype confers immunological resistance. Weisburg, J.H., Curcio, M., Caron, P.C., Raghu, G., Mechetner, E.B., Roepe, P.D., Scheinberg, D.A. J. Exp. Med. (1996) [Pubmed]
  29. The immune environment in human endometrium during the window of implantation. Lobo, S.C., Huang, S.T., Germeyer, A., Dosiou, C., Vo, K.C., Tulac, S., Nayak, N.R., Giudice, L.C. Am. J. Reprod. Immunol. (2004) [Pubmed]
  30. Demonstration of a human pyrogen-inducing factor during mixed leukocyte reactions. Dinarello, C.A. J. Exp. Med. (1981) [Pubmed]
  31. Processing, subcellular localization, and function of 519 (granulysin), a human late T cell activation molecule with homology to small, lytic, granule proteins. Peña, S.V., Hanson, D.A., Carr, B.A., Goralski, T.J., Krensky, A.M. J. Immunol. (1997) [Pubmed]
  32. A TNF family member LIGHT transduces costimulatory signals into human T cells. Wan, X., Zhang, J., Luo, H., Shi, G., Kapnik, E., Kim, S., Kanakaraj, P., Wu, J. J. Immunol. (2002) [Pubmed]
  33. Sequence analysis of the granulysin and granzyme B genes in familial hemophagocytic lymphohistiocytosis. Ericson, K.G., Fadeel, B., Andersson, M., Gudmundsson, G.H., Gürgey, A., Yalman, N., Janka, G., Nordenskjöld, M., Henter, J.I. Hum. Genet. (2003) [Pubmed]
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