Abstract
ST2 gene products that are members of IL-1 receptor family are expressed in various cells such as growth-stimulated fibroblasts and Th2 helper T-cells, and recently, IL-33, which belongs to IL-1 family, was identified as the ligand for ST2L, the receptor type product of the ST2 gene. Subsequently, IL-33 and ST2L have been reported to be involved in Th2 immunity and inflammation, however, their functions on non-immunological cells are still obscure. Among non-immunological adhesive cells, vascular endothelial cells were reported to express both ST2 gene products and IL-33, therefore, we investigated the expression manner of the ST2 gene in vascular endothelial cells and the effect of IL-33 on endothelial cells. ST2 gene was expressed in each of the vascular endothelial cell types tested, and the expression was growth-dependent and down-regulated when the cells were differentiated to form vascular structures on the extracellular membrane matrix. IL-33 scarcely affected the growth and tube formation of the endothelial cells, but induced IL-6 and IL-8 secretion from endothelial cells with the rapid activation of extracellular signal-regulated kinase (ERK) 1/2, so IL-33 is supposed to involve in inflammatory reaction of vascular endothelial cells through its receptor, ST2L.
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References
Tominaga S (1989) A putative protein of a growth specific cDNA from BALB/c-3T3 cells is highly similar to the extracellular portion of mouse interleukin 1 receptor. FEBS Lett 258:301–304
Werenskiold AK, Hoffmann S, Klemenz R (1989) Induction of a mitogen-responsive gene after expression of the Ha-ras oncogene in NIH 3T3 fibroblasts. Mol Cell Biol 9:5207–5214
Superti-Furga G, Bergers G, Picard D, Busslinger M (1991) Hormone-dependent transcriptional regulation and cellular transformation by Fos-steroid receptor fusion proteins. Proc Natl Acad Sci USA 88:5114–5118
Lanahan A, Williams JB, Sanders LK, Nathans D (1992) Growth factor-induced delayed early response gene. Mol Cell Biol 12:3919–3929
Bergers G, Reikerstorfer A, Braselmann S, Graninger P, Busslinger M (1994) Alternative promoter usage of the Fos-responsive gene Fit-1 generates mRNA isoforms coding for either secreted or membrane-bound proteins related to the IL-1 receptor. EMBO J 13:1176–1188
Yanagisawa K, Takagi T, Tsukamoto T, Tetsuka T, Tominaga S (1993) Presence of a novel primary response gene ST2L, encoding a product highly similar to the interleukin 1 receptor type 1. FEBS Lett 22:83–87
Li H, Tago K, Io K, Kuroiwa K, Arai T, Iwahana H, Tominaga S, Yanagisawa K (2000) The cloning and nucleotide sequence of human ST2L cDNA. Genomics 67:284–290
Tominaga S, Kuroiwa K, Tago K, Iwahana H, Yanagisawa K, Komatsu N (1999) Presence and expression of a novel variant form of ST2 gene product in human leukemic cell line UT-7/GM. Biochem Biophys Res Commun 264:14–18
Iwahana H, Hayakawa M, Kuroiwa Tago K, Yanagisawa K, Noji S, Tominaga S (2004) Molecular cloning of the chicken ST2 gene and a novel variant form of the ST2 gene product, ST2LV. Biochim Biophys Acta 1681:1–14
McMahan CJ, Slack JL, Mosley B, Cosman D, Lupton SD, Brunton LL, Grubin CE, Wignall JM, Jenkins NA, Brannan CI, Copeland NG, Huebner K, Croce CM, Cannizzarro LA, Benjamin D, Dower SK, Spriggs MK, Sims JE (1991) A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types. EMBO J 10:2821–2832
Kumar S, Minnich MD, Young PR (1995) ST2/T1 protein functionally binds to two secreted proteins from Balb/c 3T3 and human umbilical vein endothelial cells but does not bind interleukin 1. J Biol Chem 270:27905–27913
Yanagisawa K, Naito Y, Kuroiwa K, Arai T, Furukawa Y, Tomizuka H, Miura Y, Kasahara T, Tetsuka T, Tominaga S (1997) The expression of ST2 gene in helper T cells and the binding of ST2 protein to myeloma-derived RPMI8226 cells. J Biochem 121:95–103
Tago K, Noda T, Hayakawa M, Iwahana H, Yanagisawa K, Yashiro T, Tominaga S (2001) Tissue distribution and subcellular localization of a variant form of the human ST2 gene product, ST2V. Biochem Biophys Res Commun 285:1377–1383
Löhning M, Stroehmann A, Coyle AJ, Grogan JL, Lin S, Gutierrez-Ramos J-C, Levinson D, Radbruch A, Kamradt T (1998) T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function. Proc Natl Acad Sci USA 95:6930–6935
Oshikawa K, Yanagisawa K, Tominaga S, Sugiyama Y (2002) ST2 protein induced by inflammatory stimuli can modulate acute lung inflammation. Biochem Biophys Res Commun 299:18–24
Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23:479–490
Baekkevold ES, Roussigné M, Yamanaka T, Johansen F-E, Jahnsen FL, Amalric F, Brandtzaeg P, Erard M, Haraldsen G, Girard J-P (2003) Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules. Am J Pathol 163:69–79
Gächter T, Werenskiold AK, Klemenz R (1996) Transcription of the interleukin-1 receptor-related T1 gene is initiated at different promoters in mast cells and fibroblasts. J Biol Chem 271:124–129
Iwahana H, Yanagisawa K, Ito-Kosaka A, Kuroiwa K, Tago K, Komatsu N, Katashima R, Itakura M, Tominaga S (1999) Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells. Eur J Biochem 264:397–406
Gächter T, Moritz DR, Gheyselinck J, Klemenz R (1998) GATA-Dependent expression of the interleukin-1 receptor-related T1 gene in mast cells. Mol Cell Biol 18:5320–5331
Hayakawa M, Yanagisawa K, Aoki S, Hayakawa H, Takezako N, Tominaga S (2005) T-helper type 2 cell-specific expression of the ST2 gene is regulated by transcription factor GATA-3. Biochim Biophys Acta 1728:53–64
Zagzag D (1995) Angiogenic growth factors in neural embryogenesis and neoplasia. Am J Pathol 146:293–309
Vernon RB, Sage EH (1995) Between molecules and morphology. Extracellular matrix and creation of vascular form. Am J Pathol 147:873–883
Bell SE, Mavila A, Salazar R, Bayless KJ, Kanagala S, Maxwell SA, Davis GE (2001) Differential gene expression during capillary morphogenesis in 3D collagen matrices: regulated expression of genes involved in basement membrane matrix assembly, cell cycle progression, cellular differentiation and G-protein signaling. J Cell Sci 114:2755–2773
Hayakawa H, Hayakawa M, Kume A, Tominaga S (2007) Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation. J Biol Chem 282:26369–26380
Acknowledgments
This study was supported in part by a grant for the 21st Century COE Program from the Ministry of Education, Culture, Science, Sports, and Technology of Japan. The authors are grateful to Ms. Reiko Izawa for her excellent technical support and clerical assistance.
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Aoki, S., Hayakawa, M., Ozaki, H. et al. ST2 gene expression is proliferation-dependent and its ligand, IL-33, induces inflammatory reaction in endothelial cells. Mol Cell Biochem 335, 75–81 (2010). https://doi.org/10.1007/s11010-009-0244-9
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DOI: https://doi.org/10.1007/s11010-009-0244-9