The TSC-mTOR Signaling Pathway Regulates the Innate Inflammatory Response

Immunity

Volumn 29, Issue 4, 2008, Pages 565-577

  Weichhart, Thomas ^a   Costantino, Giuseppina ^b   Poglitsch, Marko ^a   Rosner, Margit ^a   Zeyda, Maximilian ^a   Stuhlmeier, Karl M ^c   Kolbe, Thomas ^b   Stulnig, Thomas M ^a   Hörl, Walter H ^a   Hengstschläger, Markus ^a   Müller, Mathias ^b   Säemann, Marcus D ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b UNIVERSITY OF VETERINARY MEDICINE   (Austria)

^c LUDWIG BOLTZMANN INSTITUTE FOR LUNG VASCULAR RESEARCH   (Austria)

Author keywords

MOLIMMUNO

Indexed keywords

CLODRONIC ACID; CYTOKINE; GAMMA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 12P40; INTERLEUKIN 23; INTERLEUKIN 6; MAMMALIAN TARGET OF RAPAMYCIN; RAPAMYCIN; STAT3 PROTEIN; TACROLIMUS; TUBERIN; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL EXPERIMENT; ARTICLE; AUTOIMMUNE DISEASE; BAGG ALBINO MOUSE; C57BL 6 MOUSE; CELL POLARITY; CELLULAR IMMUNITY; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DENDRITIC CELL; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HUMAN CELL; IN VIVO STUDY; INNATE IMMUNITY; LISTERIA MONOCYTOGENES; LISTERIOSIS; MACROPHAGE; MONOCYTE; MOUSE; NONHUMAN; ORGAN TRANSPLANTATION; PRIORITY JOURNAL; TH1 CELL; VACCINATION;

ANIMALS; ANTI-BACTERIAL AGENTS; CYTOKINES; FEMALE; HUMANS; IMMUNITY, INNATE; INFLAMMATION; LIPOPOLYSACCHARIDES; LISTERIA INFECTIONS; LISTERIA MONOCYTOGENES; MICE; MICE, INBRED BALB C; MICE, KNOCKOUT; MONOCYTES; NF-KAPPA B; PROTEIN KINASES; SIGNAL TRANSDUCTION; SIROLIMUS; STAT3 TRANSCRIPTION FACTOR; TH1 CELLS; TUBEROUS SCLEROSIS; TUMOR SUPPRESSOR PROTEINS;

EID: 54949109311     PISSN: 10747613     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.immuni.2008.08.012     Document Type: Article

References (47)

1. Arbibe L., Mira J.P., Teusch N., Kline L., Guha M., Mackman N., Godowski P.J., Ulevitch R.J., and Knaus U.G. Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway. Nat. Immunol. 1 (2000) 533-540
2. Benkhart E.M., Siedlar M., Wedel A., Werner T., and Ziegler-Heitbrock H.W. Role of Stat3 in lipopolysaccharide-induced IL-10 gene expression. J. Immunol. 165 (2000) 1612-1617
3. Chang E.Y., Guo B., Doyle S.E., and Cheng G. Cutting edge: Involvement of the type I IFN production and signaling pathway in lipopolysaccharide-induced IL-10 production. J. Immunol. 178 (2007) 6705-6709
4. Cheng F., Wang H.W., Cuenca A., Huang M., Ghansah T., Brayer J., Kerr W.G., Takeda K., Akira S., Schoenberger S.P., et al. A critical role for Stat3 signaling in immune tolerance. Immunity 19 (2003) 425-436
5. Colina R., Costa-Mattioli M., Dowling R.J., Jaramillo M., Tai L.H., Breitbach C.J., Martineau Y., Larsson O., Rong L., Svitkin Y.V., et al. Translational control of the innate immune response through IRF-7. Nature 452 (2008) 323-328
6. Dai W.J., Kohler G., and Brombacher F. Both innate and acquired immunity to Listeria monocytogenes infection are increased in IL-10-deficient mice. J. Immunol. 158 (1997) 2259-2267
7. Dittrich E., Schmaldienst S., Soleiman A., Horl W.H., and Pohanka E. Rapamycin-associated post-transplantation glomerulonephritis and its remission after reintroduction of calcineurin-inhibitor therapy. Transpl. Int. 17 (2004) 215-220
8. Dong C., Davis R.J., and Flavell R.A. MAP kinases in the immune response. Annu. Rev. Immunol. 20 (2002) 55-72
9. Faivre S., Kroemer G., and Raymond E. Current development of mTOR inhibitors as anticancer agents. Nat. Rev. Drug Discov. 5 (2006) 671-688
10. Fukao T., Tanabe M., Terauchi Y., Ota T., Matsuda S., Asano T., Kadowaki T., Takeuchi T., and Koyasu S. PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat. Immunol. 3 (2002) 875-881
11. Ghosh S., Tergaonkar V., Rothlin C.V., Correa R.G., Bottero V., Bist P., Verma I.M., and Hunter T. Essential role of tuberous sclerosis genes TSC1 and TSC2 in NF-kappaB activation and cell survival. Cancer Cell 10 (2006) 215-226
12. Guba M., von Breitenbuch P., Steinbauer M., Koehl G., Flegel S., Hornung M., Bruns C.J., Zuelke C., Farkas S., Anthuber M., et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: Involvement of vascular endothelial growth factor. Nat. Med. 8 (2002) 128-135
13. Halloran P.F. Immunosuppressive drugs for kidney transplantation. N. Engl. J. Med. 351 (2004) 2715-2729
14. Hay N., and Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 18 (2004) 1926-1945
15. Huang S., Bjornsti M.A., and Houghton P.J. Rapamycins: Mechanism of action and cellular resistance. Cancer Biol. Ther. 2 (2003) 222-232
16. Inoki K., Li Y., Zhu T., Wu J., and Guan K.L. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat. Cell Biol. 4 (2002) 648-657
17. Izzedine H., Brocheriou I., and Frances C. Post-transplantation proteinuria and sirolimus. N. Engl. J. Med. 353 (2005) 2088-2089
18. Karras J.G., Wang Z., Huo L., Howard R.G., Frank D.A., and Rothstein T.L. Signal transducer and activator of transcription-3 (STAT3) is constitutively activated in normal, self-renewing B-1 cells but only inducibly expressed in conventional B lymphocytes. J. Exp. Med. 185 (1997) 1035-1042
19. Kimbrell D.A., and Beutler B. The evolution and genetics of innate immunity. Nat. Rev. Genet. 2 (2001) 256-267
20. Lee D.F., Kuo H.P., Chen C.T., Hsu J.M., Chou C.K., Wei Y., Sun H.L., Li L.Y., Ping B., Huang W.C., et al. IKKbeta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway. Cell 130 (2007) 440-455
21. Lin Y.Z., Yao S.Y., Veach R.A., Torgerson T.R., and Hawiger J. Inhibition of nuclear translocation of transcription factor NF-kappa B by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence. J. Biol. Chem. 270 (1995) 14255-14258
22. Manning B.D., Tee A.R., Logsdon M.N., Blenis J., and Cantley L.C. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol. Cell 10 (2002) 151-162
23. Martin M., Schifferle R.E., Cuesta N., Vogel S.N., Katz J., and Michalek S.M. Role of the phosphatidylinositol 3 kinase-Akt pathway in the regulation of IL-10 and IL-12 by Porphyromonas gingivalis lipopolysaccharide. J. Immunol. 171 (2003) 717-725
24. Mayo M.W., Madrid L.V., Westerheide S.D., Jones D.R., Yuan X.J., Baldwin Jr. A.S., and Whang Y.E. PTEN blocks tumor necrosis factor-induced NF-kappa B-dependent transcription by inhibiting the transactivation potential of the p65 subunit. J. Biol. Chem. 277 (2002) 11116-11125
25. Miller J.L. Sirolimus approved with renal transplant indication. Am. J. Health Syst. Pharm. 56 (1999) 2177-2178
26. Monti P., Mercalli A., Leone B.E., Valerio D.C., Allavena P., and Piemonti L. Rapamycin impairs antigen uptake of human dendritic cells. Transplantation 75 (2003) 137-145
27. Mordue D.G., and Sibley L.D. A novel population of Gr-1+-activated macrophages induced during acute toxoplasmosis. J. Leukoc. Biol. 74 (2003) 1015-1025
28. Paul E., and Thiele E. Efficacy of sirolimus in treating tuberous sclerosis and lymphangioleiomyomatosis. N. Engl. J. Med. 358 (2008) 190-192
29. Perkins N.D. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat. Rev. Mol. Cell Biol. 8 (2007) 49-62
30. Rocha S., Campbell K.J., and Perkins N.D. p53- and Mdm2-independent repression of NF-kappa B transactivation by the ARF tumor suppressor. Mol. Cell 12 (2003) 15-25
31. Rosner M., and Hengstschlager M. Cytoplasmic and nuclear distribution of the protein complexes mTORC1 and mTORC2: Rapamycin triggers dephosphorylation and delocalisation of the mTORC2 components rictor and sin1. Hum. Mol. Genet. (2008) 10.1093/hmg/ddn192 Published online July 8, 2008
32. Saemann M.D., Weichhart T., Zeyda M., Staffler G., Schunn M., Stuhlmeier K.M., Sobanov Y., Stulnig T.M., Akira S., von Gabain A., et al. Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a Toll-like receptor-4-dependent mechanism. J. Clin. Invest. 115 (2005) 468-475
33. Salcedo R., Ponce M.L., Young H.A., Wasserman K., Ward J.M., Kleinman H.K., Oppenheim J.J., and Murphy W.J. Human endothelial cells express CCR2 and respond to MCP-1: Direct role of MCP-1 in angiogenesis and tumor progression. Blood 96 (2000) 34-40
34. Sarbassov D.D., Ali S.M., Sengupta S., Sheen J.H., Hsu P.P., Bagley A.F., Markhard A.L., and Sabatini D.M. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol. Cell 22 (2006) 159-168
35. Schust J., Sperl B., Hollis A., Mayer T.U., and Berg T. Stattic: A small-molecule inhibitor of STAT3 activation and dimerization. Chem. Biol. 13 (2006) 1235-1242
36. Seki E., Tsutsui H., Tsuji N.M., Hayashi N., Adachi K., Nakano H., Futatsugi-Yumikura S., Takeuchi O., Hoshino K., Akira S., et al. Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice. J. Immunol. 169 (2002) 3863-3868
37. Sekulic A., Hudson C.C., Homme J.L., Yin P., Otterness D.M., Karnitz L.M., and Abraham R.T. A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells. Cancer Res. 60 (2000) 3504-3513
38. Singer S.J., Tiernan R., and Sullivan E.J. Interstitial pneumonitis associated with sirolimus therapy in renal-transplant recipients. N. Engl. J. Med. 343 (2000) 1815-1816
39. Strobl B., Bubic I., Bruns U., Steinborn R., Lajko R., Kolbe T., Karaghiosoff M., Kalinke U., Jonjic S., and Muller M. Novel functions of tyrosine kinase 2 in the antiviral defense against murine cytomegalovirus. J. Immunol. 175 (2005) 4000-4008
40. Taner T., Hackstein H., Wang Z., Morelli A.E., and Thomson A.W. Rapamycin-treated, alloantigen-pulsed host dendritic cells induce ag-specific T cell regulation and prolong graft survival. Am. J. Transplant. 5 (2005) 228-236
41. Thaunat O., Beaumont C., Chatenoud L., Lechaton S., Mamzer-Bruneel M.F., Varet B., Kreis H., and Morelon E. Anemia after Late Introduction of Sirolimus May Correlate with Biochemical Evidence of a Chronic Inflammatory State. Transplantation 80 (2005) 1212-1219
42. Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat. Rev. Immunol. 3 (2003) 133-146
43. Tripp C.S., Gately M.K., Hakimi J., Ling P., and Unanue E.R. Neutralization of IL-12 decreases resistance to Listeria in SCID and C.B-17 mice. Reversal by IFN-gamma. J. Immunol. 152 (1994) 1883-1887
44. Wullschleger S., Loewith R., and Hall M.N. TOR signaling in growth and metabolism. Cell 124 (2006) 471-484
45. Yang C.S., Song C.H., Lee J.S., Jung S.B., Oh J.H., Park J., Kim H.J., Park J.K., Paik T.H., and Jo E.K. Intracellular network of phosphatidylinositol 3-kinase, mammalian target of the rapamycin/70 kDa ribosomal S6 kinase 1, and mitogen-activated protein kinases pathways for regulating mycobacteria-induced IL-23 expression in human macrophages. Cell. Microbiol. 8 (2006) 1158-1171
46. Yang Q., and Guan K.L. Expanding mTOR signaling. Cell Res. 17 (2007) 666-681
47. Ziegler-Heitbrock L., Lotzerich M., Schaefer A., Werner T., Frankenberger M., and Benkhart E. IFN-alpha induces the human IL-10 gene by recruiting both IFN regulatory factor 1 and Stat3. J. Immunol. 171 (2003) 285-290