Molecular Mechanisms Governing IL-24 Gene Expression

다국어 초록 (Multilingual Abstract)

Interleukin-24 (IL-24) belongs to the IL-10 family of cytokines and is well known for its tumor suppressor activity. This cytokine is released by both immune and nonimmune cells and acts on non-hematopoietic tissues such as skin, lung and reproductive tissues. Apart from its ubiquitous tumor suppressor function, IL-24 is also known to be involved in the immunopathology of autoimmune diseases like psoriasis and rheumatoid arthritis. Although the cellular sources and functions of IL-24 are being increasingly investigated, the molecular mechanisms of IL-24 gene expression at the levels of signal transduction, epigenetics and transcription factor binding are still unclear. Understanding the specific molecular events that regulate the production of IL-24 will help to answer the remaining questions that are important for the design of new strategies of immune intervention involving IL-24. Herein, we briefly review the signaling pathways and transcription factors that facilitate, induce, or repress production of this cytokine along with the cellular sources and functions of IL-24.

참고문헌 (Reference)

1 Dash R, "mda-7/IL-24: a unique member of the IL-10 gene family promoting cancer-targeted toxicity" 21 : 381-391, 2010

2 이석근, "mda-7/IL-24, novel anticancer cytokine: Focus on bystander antitumor, radiosensitization and antiangiogenic properties and overview of the phase I clinical experience (Review)" PROFESSOR D A SPANDIDOS 31 (31): 985-1007, 200711

3 Sarkar D, "mda-7 (IL-24) Mediates selective apoptosis in human melanoma cells by inducing the coordinated overexpression of the GADD family of genes by means of p38 MAPK" 99 : 10054-10059, 2002

4 Dumoutier L, "Viral and cellular interleukin-10(IL-10)-related cytokines: from structures to functions" 13 : 5-15, 2002

5 Sieger KA, "The tumor suppressor activity of MDA-7/IL-24 is mediated by intracellular protein expression in NSCLC cells" 9 : 355-367, 2004

6 Saraiva M, "The regulation of IL-10 production by immune cells" 10 : 170-181, 2010

7 Caudell EG, "The protein product of the tumor suppressor gene, melanoma differentiation-associated gene 7, exhibits immunostimulatory activity and is designated IL-24" 168 : 6041-6046, 2002

8 Otkjaer K, "The p38 MAPK regulates IL-24 expression by stabilization of the 3' UTR of IL-24 mRNA" 5 : e8671-, 2010

9 Jiang H, "The melanoma differentiation associated gene mda-7 suppresses cancer cell growth" 93 : 9160-9165, 1996

10 Schübeler D, "The histone modification pattern of active genes revealed through genome- wide chromatin analysis of a higher eukaryote" 18 : 1263-1271, 2004

11 Kragstrup TW, "The expression of IL-20 and IL-24 and their shared receptors are increased in rheumatoid arthritis and spondyloarthropathy" 41 : 16-23, 2008

12 Reinemer P, "The Interleukin-4-Recep tor: From Recognition Mechanism to Pharmacological Target Structure" 39 : 2834-2846, 2000

13 Lee GR, "T helper cell differentiation: regulation by cis elements and epigenetics" 24 : 369-379, 2006

14 Jiang H, "Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression" 11 : 2477-2486, 1995

15 Rennick DM, "Studies with IL-10-/- mice: an overview" 61 : 389-396, 1997

16 Sahoo A, "Stat6 and c-Jun mediate Th2 cell-specific IL-24 gene expression" 186 : 4098-4109, 2011

17 Li-Weber M, "Regulation of IL4 gene expression by T cells and therapeutic perspectives" 3 : 534-443, 2003

18 Glimcher LH, "Recent developments in the transcriptional regulation of cytolytic effector cells" 4 : 900-911, 2004

19 Zhou L, "Plasticity of CD4＋ T cell lineage differentiation" 30 : 646-655, 2009

20 Dalton DK, "Multiple defects of immune cell function in mice with disrupted interferon-gamma genes" 259 : 1739-1742, 1993

21 Miyahara R, "Melanoma differentiation-associated gene-7 (mda-7)/interleukin (IL)-24 induces anticancer immunity in a syngeneic murine model" 13 : 753-761, 2006

22 Ramesh R, "Melanoma differentiation- associated gene 7/interleukin (IL)-24 is a novel ligand that regulates angiogenesis via the IL-22 receptor" 63 : 5105-5113, 2003

23 Lebedeva IV, "Melanoma differentiation associated gene-7, mda-7/interleukin-24, induces apoptosis in prostate cancer cells by promoting mitochondrial dysfunction and inducing reactive oxygen species" 63 : 8138-8144, 2003

24 Mhashilkar AM, "Melanoma differentiation associated gene-7 (mda-7): a novel anti-tumor gene for cancer gene therapy" 7 : 271-282, 2001

25 Sauane M, "MDA-7/IL-24: novel cancer growth suppressing and apoptosis inducing cytokine" 14 : 35-51, 2003

26 Chada S, "MDA-7/IL-24 is a unique cytokine--tumor suppressor in the IL-10 family" 4 : 649-667, 2004

27 Ellerhorst JA, "Loss of MDA-7 expression with progression of melanoma" 20 : 1069-1074, 2002

28 Fisher PB, "Is mda-7/IL-24 a “magic bullet” for cancer?" 65 : 10128-10138, 2005

29 Wang M, "Interleukin24 (MDA-7/MOB-5) signals through two heterodimeric receptors,IL-22R1/IL-20R2 and IL-20R1/IL-20R2" 277 : 7341-7347, 2002

30 Maarof G, "Interleukin-24 inhibits the plasma cell differentiation program in human germinal center B cells" 115 : 1718-1726, 2010

31 Wang M, "Interleukin-24 and its receptors" 114 : 166-170, 2005

32 Kunz S, "Interleukin (IL)-19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs" 15 : 991-1004, 2006

33 Schroder K, "Interferongamma: an overview of signals, mechanisms and functions" 75 : 163-189, 2004

34 Lebedeva IV, "Induction of reactive oxygen species renders mutant and wild-type K-ras pancreatic carcinoma cells susceptible to Ad.mda-7-induced apoptosis" 24 : 585-596, 2005

35 Ricci M, "IL-4 as a key factor influencing the development of allergen-specific Th2-like cells in atopic individuals" 7 : 144-150, 1997

36 Kreis S, "IL-24: a classic cytokine and/or a potential cure for cancer?" 12 : 2505-2510, 2008

37 He M, "IL-24 transgenic mice: in vivo evidence of overlapping functions for IL-20, IL-22, and IL-24 in the epidermis" 184 : 1793-1798, 2010

38 Wolk K, "IL-22 increases the innate immunity of tissues" 21 : 241-254, 2004

39 Wahl C, "IL-20 receptor 2 signaling down-regulates antigen-specific T cell responses" 182 : 802-810, 2009

40 Pan L, "HDAC4 inhibits the transcriptional activation of mda-7/IL-24 induced by Sp1" 7 : 221-226, 2010

41 Huang EY, "Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties" 20 : 7051-7063, 2001

42 Andoh A, "Expression of IL-24, an activator of the JAK1/STAT3/SOCS3 cascade, is enhanced in inflammatory bowel disease" 183 : 687-695, 2009

43 Egger G, "Epigenetics in human disease and prospects for epigenetic therapy" 429 : 457-463, 2004

44 Sharma S, "Epigenetics in cancer" 31 : 27-36, 2010

45 Zou YR, "Epigenetic silencing of CD4 in T cells committed to the cytotoxic lineage" 29 : 332-336, 2001

46 Choong-Gu Lee, "Epigenetic Regulation of Cytokine Gene Expression in T Lymphocytes" 연세대학교의과대학 50 (50): 322-330, 2009

47 Rømer J, "Epidermal overexpression of interleukin- 19 and -20 mRNA in psoriatic skin disappears after short-term treatment with cyclosporine a or calcipotriol" 121 : 1306-1311, 2003

48 Ramesh R, "Ectopic production of MDA-7/IL-24 inhibits invasion and migration of human lung cancer cells" 9 : 510-518, 2004

49 Liu X, "Duration of TCR signaling controls CD4-CD8 lineage differentiation in vivo" 5 : 280-288, 2004

50 Wei L, "Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation" 32 : 840-851, 2010

51 Madireddi MT, "Dent P" 19 : 1362-1368, 2000

52 Wolk K, "Cutting edge: immune cells as sources and targets of the IL-10 family members?" 168 : 5397-5402, 2002

53 Schaefer G, "Cutting edge: FISP (IL-4-induced secreted protein), a novel cytokine-like molecule secreted by Th2 cells" 166 : 5859-5863, 2001

54 Soo C, "Cutaneous rat wounds express c49a, a novel gene with homology to the human melanoma differentiation associated gene, mda-7" 74 : 1-10, 1999

55 Fischer JJ, "Combinatorial effects of four histone modifications in transcription and differentiation" 91 : 41-51, 2008

56 Cunningham CC, "Clinical and local biological effects of an intratumoral injection of mda-7 (IL24; INGN 241) in patients with advanced carcinoma: a phase I study" 11 : 149-159, 2005

57 임신혁, "Chromatin-level regulation of the IL10 gene in T cells" AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 279 (279): 46818-46825, 200411

58 Boehm U, "Cellular responses to interferon-gamma" 15 : 749-795, 1997

59 Gupta P, "BiP/GRP78 is an intracellular target for MDA-7/IL-24 induction of cancer- specific apoptosis" 66 : 8182-8191, 2006

60 Phan RT, "BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells" 6 : 1054-1060, 2005

61 Ansel KM, "An epigenetic view of helper T cell differentiation" 4 : 616-623, 2003

62 Workman JL, "Alteration of nucleosome structure as a mechanism of transcriptional regulation" 67 : 545-579, 1998

63 Madireddi MT, "AP-1 and C/EBP transcription factors contribute to mda-7 gene promoter activity during human melanoma differentiation" 185 : 36-46, 2000