Cytokine gene

Messi M, Giacchetto I, Nagata K, Lanzavecchia A, Natoli G, Sallusto F. Memory and flexibility of cytokine gene expression as separable properties of human T(H)1 and T(H)2 lymphocytes. Nat Immunol 2003 4 78-86. 

Bidwell J et al. Cytokine gene polymorphism in human disease on-line databases. Genes Immun 1999 1[1] 3—19. 

Analysis of cytokine genes established the exact evolutionary relationships between these molecules. 

Worth, L.L. et al., ImmTher, a lipophilic disaccharide derivative of muramyl dipeptide, up-regulates specific monocyte cytokine genes and activates monocyte- mediated tumoricidal activity, Cancer Immunol Immunother., 48, 312, 1999. 

Integrated In Vivo Model for Cytokine Gene Expression.296... 

Betts, C J. et al., Temporal changes in cytokine gene expression profiles induced in mice by trimellitic anhydride. Tox. Lett., 136, 121, 2002. 

G-CSF expression is controlled at both the transcriptional and posttranscrip-tional levels. A sequence of 300 nucleotides upstream of the initiation codon is conserved in both the murine and human genes, and this appears to contain three regulatory sites. G-CSF (and some other cytokine genes) may be constitutively transcribed by cells such as blood monocytes, fibroblasts and endothelial cells, but the mRNA may be short-lived (fi/2 < 15 min). The mRNA contains poly-AUUUA sequences in the untranslated region, and this motif is usually associated with mRNA instability. Indeed, such regions have also been identified in mRNA for GM-CSF, IL-1, IL-6, interferons, TNF, some growth factors, c-jun, c-fos, c-myc and c-myb. Upon the addi-... 

Th2 cells selectively express IL-21 in addition to the classic Th2 cytokines IL-4, IL-5, and IL-13. In contrast to these clustered Th2 cell cytokine genes, the IL-21 gene resides on a different... 

Kanangat S, Blair P, Reddy R, Daheshia M, Godfrey V, Rouse BT, et al Disease in the Scurfy mouse is associated with overexpression of cytokine genes. Eur J Immunol 1996 26 161-165. 

Figure 2 Cytokine gene expression in immunopotentiating reconstituted influenza virosomes (IRIV) stimulated peripheral blood mononuclear cells (PBMC). PBMC were cultured in the presence or absence of IRIV. On days 1 and 2, culture cells were harvested and total cellular RNA was extracted and reverse transcribed. The cDNAs thus obtained were tested in real time polymerase chain reaction assays in the presence of primers specific for the indicated cytokine genes. Source From Refs. 6 and 9.

Filgueira L, Zuber M, Juretic A, et al. Differential effects of interleukin-2 and CD3 triggering on cytokine gene transcription and secretion in cultured tumor infiltrating lymphocytes. Cell Immunol 1993 150 205. 

Bucy, R.P., Panoskaltsis-Mortari, A., Huang, G., et al. (1994) Heterogenicity of single cell cytokine gene expression in clonal T cell populations. J. Exp. Med. 180, 1251-1262. 

Canete ID, Llena J, Collado A, Sanmarti R, Gaya A, Gratacos J et al. Comparative cytokine gene expression in synovial tissue of early rheumatoid arthritis... 

Nakano, A., A. Matsumori, S. Kawamoto, H. Tahara, E. Yamato, S. Sasayama, and J.I. Miyazaki, Cytokine gene therapy for myocarditis by in vivo electroporation. Hum Gene Ther, 2001.12(10) 1289-97. 

Lee JS, Campbell HD, Kozak CA, Young IG. 1989. The IL-4 and IL-5 genes are closely linked and are part of a cytokine gene cluster on mouse chromosome 11. Somat Cell Mol Genet. 15 143-152. 

Van Leeuwen BH, Martinson ME, Webb GC, Young IG. 1989. Molecular organization of the cytokine gene cluster, involving the human IL-3, IL-4, IL-5 and GM-CSF genes, on human chromosome 5. Blood. 73 1142-1148. 

Fig. 4.1 Mechanism of action of cyclosporine. Cyclosporine readily diffuses into the cytoplasm of the target cells where it binds to cyclophilins. The cyclosporine-cyclophilin complex stably associates with calcineurin and inhibits calcineurin activity. Calcineurin is a Ca2+-dependent enzyme— serine/threonine phosphatase— which after activation by Ca2+, dephosphorylates a cytosolic component of NFAT (NFATc, cytosolic factor of activated T cells). After dephosphorylation, NFATc migrates from the cytoplasm to the nucleus where it associates with NFATn and induces transcription of several cytokine genes including IL-2. Cyclosporine inhibits calcineurin activity after associating with cyclophilins, resulting in the inhibition of IL-2 production and other cytokines (see Color Insert)...

Tacrolimus suppresses peptidyl-prolyl isomerase activity by binding to the immuno-philin FK506-binding protein-12 (FKBP-12), and the tacrolimus-FKBP-12 complex binds to calcineurin and inhibits calcineurin phosphatase activity. As a result, calcineurin is unable to dephosphorylate NFATc and thus its migration to nucleus is blocked where its association with NFATn is necessary for the activation of key cytokine genes. Therefore, its mechanism of action is similar to cyclosporine although tacrolimus binds to a separate set of immunophilins in the cytoplasm. Tacrolimus, like cyclosporine, inhibits the secretion of key cytokines and inhibits T-cell activation (Fig. 4.2). 

Scheerlinck, J.P., Casey, G., McWaters, P., Kelly, J., Woollard, D., Lightowlers, M.W., Tennent, J.M. and Chaplin, P.J. (2001) The immune response to a DNA vaccine can be modulated by co-delivery of cytokine genes using a DNA prime-protein boost strategy. Vaccine 19, 4053-4060. 

Hamid Q, Boguniewicz M, Leung DYM Differential cytokine gene expression in acute vs chronic atopic dermatitis. J Clin Invest 1994 94 870-876. 

Mucke, S., Draube, A., Polack, A., Pawlita, M., Massoud, N., Staratschek-Jox, A. et al. (2000) Suppression of the tumorigenic growth of Burkitf s lymphoma cells in immunodeficient mice by cytokine gene transfer using EBV-derived episomal expression vectors. Int.J. Cancer, 86, 301-306. 

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