| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
IL-12 is a heterodimer of two subunits, p35 and p40, encoded by separate genes that are regulated independently. To investigate the mechanisms underlying the regulation of the p35 gene, we characterized murine p35 expression in the B cell lymphoma line A20 and in bone marrow-derived dendritic cells. Multiple transcription start sites were identified in both cell types, resulting in four p35 mRNA isoforms (types I–IV) that differ in the number and position of upstream ATGs in their 5' untranslated regions. In nonstimulated cells, the predominant forms of p35 message (types II and IV) contained an additional upstream ATG, whose presence was shown to inhibit the downstream translation of the p35 subunit. After LPS stimulation, however, transcription initiated from alternate positions, so that the proportion of transcripts not containing this upstream ATG (types I and III) was significantly increased in the population of p35 mRNA. These type I and type III transcripts readily supported translation of the p35 subunit and its incorporation into bioactive IL-12. Furthermore, p35 mRNA levels were substantially up-regulated after LPS stimulation in both cell types. Thus, our results show that p35 gene expression is highly regulated by both transcriptional and translational mechanisms.
This article has been cited by other articles:
|
|
 |
|
  C. Rival, V. A. Guazzone, W. von Wulffen, H. Hackstein, E. Schneider, L. Lustig, A. Meinhardt, and M. Fijak Expression of co-stimulatory molecules, chemokine receptors and proinflammatory cytokines in dendritic cells from normal and chronically inflamed rat testis Mol. Hum. Reprod., December 1, 2007; 13(12): 853 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Heo, T. K. Mondal, D. Gao, J. Kasten-Jolly, H. Kishikawa, and D. A. Lawrence Posttranscriptional Inhibition of Interferon-Gamma Production by Lead Toxicol. Sci., March 1, 2007; 96(1): 92 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Saito, M. Matsuura, and Y. Hirai Regulation of Lipopolysaccharide-Induced Interleukin-12 Production by Activation of Repressor Element GA-12 through Hyperactivation of the ERK Pathway. Clin. Vaccine Immunol., August 1, 2006; 13(8): 876 - 883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Liu, X. Guan, T. Tamura, K. Ozato, and X. Ma Synergistic Activation of Interleukin-12 p35 Gene Transcription by Interferon Regulatory Factor-1 and Interferon Consensus Sequence-binding Protein J. Biol. Chem., December 31, 2004; 279(53): 55609 - 55617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Stassen, H. Jonuleit, C. Muller, M. Klein, C. Richter, T. Bopp, S. Schmitt, and E. Schmitt Differential Regulatory Capacity of CD25+ T Regulatory Cells and Preactivated CD25+ T Regulatory Cells on Development, Functional Activation, and Proliferation of Th2 Cells J. Immunol., July 1, 2004; 173(1): 267 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sheng, C.-H. Tsai-Morris, and M. L. Dufau Cell-specific and Hormone-regulated Expression of Gonadotropin-regulated Testicular RNA Helicase Gene (GRTH/Ddx25) Resulting from Alternative Utilization of Translation Initiation Codons in the Rat Testis J. Biol. Chem., July 18, 2003; 278(30): 27796 - 27803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Goriely, D. Demonte, S. Nizet, D. De Wit, F. Willems, M. Goldman, and C. Van Lint Human IL-12(p35) gene activation involves selective remodeling of a single nucleosome within a region of the promoter containing critical Sp1-binding sites Blood, June 15, 2003; 101(12): 4894 - 4902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mirani, I. Elenkov, S. Volpi, N. Hiroi, G. P. Chrousos, and T. Kino HIV-1 Protein Vpr Suppresses IL-12 Production from Human Monocytes by Enhancing Glucocorticoid Action: Potential Implications of Vpr Coactivator Activity for the Innate and Cellular Immunity Deficits Observed in HIV-1 Infection J. Immunol., December 1, 2002; 169(11): 6361 - 6368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. D. Joshi, D. V. Kalvakolanu, J. D. Hasday, R. J. Hebel, and A. S. Cross IL-18 Levels and the Outcome of Innate Immune Response to Lipopolysaccharide: Importance of a Positive Feedback Loop with Caspase-1 in IL-18 Expression J. Immunol., September 1, 2002; 169(5): 2536 - 2544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kozak Constraints on reinitiation of translation in mammals Nucleic Acids Res., December 15, 2001; 29(24): 5226 - 5232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kollet, C. Witek, J. D. Gentry, X. Liu, S. D. Schwartzbach, and T. M. Petro Deletional Analysis of the Murine IL-12 p35 Promoter Comparing IFN-{gamma} and Lipopolysaccharide Stimulation J. Immunol., November 15, 2001; 167(10): 5653 - 5663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Qadir, A. Metwali, A. M. Blum, J. Li, D. E. Elliott, and J. V. Weinstock TGF-beta and IL-10 regulation of IFN-gamma produced in Th2-type schistosome granulomas requires IL-12 Am J Physiol Gastrointest Liver Physiol, October 1, 2001; 281(4): G940 - G946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Goodridge, E. H. Wilson, W. Harnett, C. C. Campbell, M. M. Harnett, and F. Y. Liew Modulation of Macrophage Cytokine Production by ES-62, a Secreted Product of the Filarial Nematode Acanthocheilonema viteae J. Immunol., July 15, 2001; 167(2): 940 - 945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Grazia Cappiello, F. S. Sutterwala, G. Trinchieri, D. M. Mosser, and X. Ma Suppression of IL-12 Transcription in Macrophages Following Fc{{gamma}} Receptor Ligation J. Immunol., April 1, 2001; 166(7): 4498 - 4506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang-Hoover, A. Sutton, and J. Stein-Streilein CD40/CD40 Ligand Interactions Are Critical for Elicitation of Autoimmune-Mediated Fibrosis in the Lung J. Immunol., March 1, 2001; 166(5): 3556 - 3563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Goriely, B. Vincart, P. Stordeur, J. Vekemans, F. Willems, M. Goldman, and D. De Wit Deficient IL-12(p35) Gene Expression by Dendritic Cells Derived from Neonatal Monocytes J. Immunol., February 1, 2001; 166(3): 2141 - 2146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Walter, N. Kajiwara, P. Karanja, M. Castro, and M. J. Holtzman Interleukin 12 p40 Production by Barrier Epithelial Cells during Airway Inflammation J. Exp. Med., January 29, 2001; 193(3): 339 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Malmgaard, S. R. Paludan, S. C. Mogensen, and S. Ellermann-Eriksen Herpes simplex virus type 2 induces secretion of IL-12 by macrophages through a mechanism involving NF-{kappa}B J. Gen. Virol., December 1, 2000; 81(12): 3011 - 3020. [Abstract] [Full Text]
|
|
|
|
|
|
M. Quinones, S. K. Ahuja, P. C. Melby, L. Pate, R. L. Reddick, and S. S. Ahuja Preformed Membrane-associated Stores of Interleukin (IL)-12 Are a Previously Unrecognized Source of Bioactive IL-12 That Is Mobilized within Minutes of Contact with an Intracellular Parasite J. Exp. Med., August 14, 2000; 192(4): 507 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tone, M. J. Powell, Y. Tone, S. A. J. Thompson, and H. Waldmann IL-10 Gene Expression Is Controlled by the Transcription Factors Sp1 and Sp3 J. Immunol., July 1, 2000; 165(1): 286 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Carra, F. Gerosa, and G. Trinchieri Biosynthesis and Posttranslational Regulation of Human IL-12 J. Immunol., May 1, 2000; 164(9): 4752 - 4761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Ulett, N. Ketheesan, and R. G. Hirst Cytokine Gene Expression in Innately Susceptible BALB/c Mice and Relatively Resistant C57BL/6 Mice during Infection with Virulent Burkholderia pseudomallei Infect. Immun., April 1, 2000; 68(4): 2034 - 2042. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
