PI3K/Akt/mTOR, a pathway less recognized for staphylococcal superantigen-induced toxicity

Toxins

Volumn 4, Issue 11, 2012, Pages 1343-1366

  Krakauer, Teresa ^a  

^a UNITED STATES ARMY MEDICAL RESEARCH INSTITUTE OF INFECTIOUS DISEASES   (United States)

Author keywords

Akt; Inflammatory cytokines; mTOR; PI3K; Signaling pathways; Staphylococcal superantigens; Therapeutics

Indexed keywords

ACETYLCYSTEINE; BORTEZOMIB; CALCINEURIN INHIBITOR; CHEMOKINE; CYCLOSPORIN A; CYTOKINE; CYTOKINE RECEPTOR; DEXAMETHASONE; GAMMA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1; INTERLEUKIN 2; JANUS KINASE 1; JANUS KINASE 2; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 13; MONOCYTE CHEMOTACTIC PROTEIN 1; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN SERINE THREONINE KINASE; PYRROLIDINE DITHIOCARBAMATE; RAPAMYCIN; STAPHYLOCOCCUS ENTEROTOXIN B; STAPHYLOCOCCUS TOXIN; STAT1 PROTEIN; SUPERANTIGEN; T LYMPHOCYTE RECEPTOR; TACROLIMUS; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG;

ANTIGEN PRESENTING CELL; ANTIGEN RECOGNITION; FEVER; HUMAN; HYPERTENSION; IMMUNE SYSTEM; IMMUNOSTIMULATION; LYMPHOCYTE ACTIVATION; MACROPHAGE; MAJOR HISTOCOMPATIBILITY COMPLEX; MONOCYTE; NONHUMAN; REVIEW; SHOCK; SIGNAL TRANSDUCTION; STAPHYLOCOCCAL SUPERANTIGEN INDUCED TOXICITY; SYMPTOMATOLOGY; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TOXICITY;

ANIMALS; ANTIBODIES, MONOCLONAL; BACTERIAL TOXINS; CYTOKINES; ENTEROTOXINS; HISTOCOMPATIBILITY ANTIGENS CLASS II; HUMANS; LYMPHOCYTE ACTIVATION; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN BINDING; PROTEIN-SERINE-THREONINE KINASES; RECEPTORS, ANTIGEN, T-CELL; SHOCK, SEPTIC; SIGNAL TRANSDUCTION; STAPHYLOCOCCUS; SUPERANTIGENS; T-LYMPHOCYTES; TOR SERINE-THREONINE KINASES;

ANIMALIA; MAMMALIA;

EID: 84870513251     PISSN: 20726651     EISSN: None     Source Type: Journal    
DOI: 10.3390/toxins4111343     Document Type: Review

References (146)

1. Chesney, P.J.; Davis, P.J.; Purdy, W.K.; Wand, P.J.; Chesney, R.W. Clinical manifestations of toxic shock syndrome. JAMA 1981, 246, 741-748.
2. Marrack, P.; Kappler, J. The staphylococcal enterotoxins and their relatives. Science 1990, 248, 705-709.
3. Kotzin, B.L.; Leung, D.Y.M.; Kappler, J.; Marrack, P. Superantigens and their potential role in human disease. Adv. Immunol. 1993, 54, 99-166.
4. Kotb, M. Bacterial pyrogenic exotoxins as superantigens. Clin. Microbiol. Rev. 1995, 8, 411-426.
5. McCormick, J.K.; Yarwood, J.M.; Schlievert, P.M. Toxic shock syndrome and bacterial superantigens: An update. Ann. Rev. Microbiol. 2001, 55, 77-104.
6. Proft, T.; Fraser, J.D. Bacterial superantigens. Clin. Exp. Immunol. 2003, 133, 299-306.
7. Fraser, J.D.; Proft, T. The bacterial superantigen and superantigen-like proteins. Immunol. Rev. 2008, 225, 226-243.
8. Choi, Y.; Kotzin, B.; Hernon, L.; Callahan, J.; Marrack, P.; Kappler, J. Interaction of Staphylococcus aureus toxin "superantigens" with human T cells. Proc. Natl. Acad. Sci. USA 1989, 86, 8941-8945.
9. Jupin, C.; Anderson, S.; Damais, C.; Alouf, J.E.; Parant, M. Toxic shock syndrome toxin 1 as an inducer of human tumor necrosis factors and gamma interferon. J. Exp. Med. 1988, 167, 752-761.
10. Trede, N.S.; Geha, R.S.; Chatila, T. Transcriptional activation of IL-1 beta and tumor necrosis factor-alpha genes by MHC class II ligands. J. Immunol. 1991, 146, 2310-2315.
11. See, R.H.; Kum, W.W.; Chang, A.H.; Goh, S.H.; Chow, A.W. Induction of tumor necrosis factor and interleukin-1 by purified staphylococcal toxic shock syndrome toxin 1 requires the presence of both monocytes and T lymphocytes. Infect. Immun. 1992, 60, 2612-2618.
12. Miethke, T.; Wahl, C.; Heeg, K.; Echtenacher, B.; Krammer, P.H.; Wagner, H. Superantigen mediated shock: A cytokine release syndrome. Immunobiology 1993, 189, 270-284.
13. Tessier, P.A.; Naccache, P.H.; Diener, K.R.; Gladue, R.P.; Neotem, K.S.; Clark-Lewis, I.; McColl, S.R. Induction of acute inflammation in vivo by staphylococcal superantigens. II. Critical role for chemokines, ICAM-1, and TNF-alpha. J. Immunol. 1998, 161, 1204-1211.
14. Krakauer, T. The induction of CC chemokines in human peripheral blood mononuclear cells by staphylococcal exotoxins and its prevention by pentoxifylline. J. Leukco. Biol. 1999, 66, 158-164.
15. Faulkner, L.; Cooper, A.; Fantino, C.; Altmann, D.M.; Sriskandan, S. The mechanism of superantigen-mediated toxic shock: Not a simple Th1 cytokine storm. J. Immunol. 2005, 175, 6870-6877.
16. Krakauer, T.; Buckley, M.; Fisher, D. Proinflammatory mediators of toxic shock and their correlation to lethality. Mediators Inflamm. 2010, doi:10.1155/2010/517594.
17. Mattsson, E.; Herwald, H.; Egsten, A. Superantigen from Staphylococcus aureus induce procoagulant activity and monocyte tissue factor expression in whole blood and mononuclear cells via IL-1β. J. Thromb. Haemost. 2003, 1, 2569-2575.
18. Neumann, B.; Engelhardt, B.; Wagner, H.; Holzmann, B. Induction of acute inflammatory lung injury by staphylococcal enterotoxin B. J. Immunol. 1997, 158, 1862-1871.
19. Miethke, T.; Wahl, C.; Heeg, K.; Echtenacher, B.; Krammer, P.H.; Wagner, H. T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: Critical role of tumor necrosis factor. J. Exp. Med. 1992, 175, 91-98.
20. Stiles, B.G.; Bavari, S.; Krakauer, T.; Ulrich, R.G. Toxicity of staphylococcal enterotoxins potentiated by lipopolysaccharide: Major histocompatibility complex class II molecule dependency and cytokine release. Infect. Immun. 1993, 61, 5333-5338.
21. Krakauer, T.; Vilcek, J.; Oppenheim, J.J. Proinflammatory Cytokines: TNF and IL-1 Families, Chemokines, TGFβ and Others. In Fundamental Immunology, 4th ed.; Paul, W., Ed.; Lippincott-Raven: Philadelphia, PA, USA, 1998; pp. 775-811.
22. Vial, T.; Descotes, J. Immune-mediated side-effects of cytokines in human. Toxicology 1995, 105, 31-57.
23. Holmberg, S.D.; Blake, P.A. Staphylococcal food poisoning in the United States. New facts and old misconceptions. JAMA 1984, 251, 487-489.
24. Schwab, J.H.; Brown, R.R.; Anderle, S.K.; Schlievert, P.M. Superantigen can reactivate bacterial cell wall-induced arthritis. J. Immunol. 1993, 150, 4151-4159.
25. Brocke, S.; Hausmann, S.; Steinmam, L.; Wucherpfennig, K.W. Microbial peptides and superantigens in the pathogenesis of autoimmune diseases of the central nervous system. Semin. Immunol. 1998, 10, 57-67.
26. Yarwood, J.M.; Leung, D.Y.; Schlievert, P.M. Evidence for the involvement of bacterial superantigens in psoriasis, atopic dermatitis, and Kawasaki syndrome. FEMS Microbiol. Lett. 2000, 192, 1-7.
27. McKay, D.M. Bacterial superantigens: Provocateurs of gut dysfunction and inflammation? Trends Immunol. 2001, 22, 497-501.
28. Sugiyama, H.; McKissic, E.M.; Bergdoll, M.S.; Heller, B. Enhancement of bacterial endotoxin lethality by staphylococcal enterotoxin. J. Infect. Dis. 1964, 4, 111-118.
29. Sarawar, S.R.; Blackman, B.A.; Doherty, P.C. Superantigen shock in mice with an inapparent viral infection. J. Infect. Dis. 1994, 170, 1189-1194.
30. Zhang, W.J.; Sarawar, S.; Nguyen, P.; Daly, K.; Rehig, J.E.; Doherty, P.C.; Woodland, D.L.; Blackman, M.A. Lethal synergism between influenza infection and staphylococcal enterotoxin B in mice. J. Immunol. 1996, 157, 5049-5060.
31. Blank, C.; Luz, A.; Bendigs, S.; Erdmann, A.; Wagner, H.; Heeg, K. Superantigen and endotoxin synergize in the induction of lethal shock. Eur. J. Immunol. 1997, 27, 825-833.
32. Hopkins, P.A.; Fraser, J.D.; Pridmore, A.C.; Russell, H.H.; Read, R.C.; Sriskandan, S. Superantigen recognition by HLA class II on monocytes up-regulates toll-like receptor 4 and enhances proinflammatory responses to endotoxin. Blood 2005, 105, 3655-3662.
33. Hopkins, P.A.; Pridmore, A.C.; Ellmerich, S.; Fraser, J.D.; Russell, H.H.; Read, R.C.; Sriskandan, S. Increased surface toll-like receptor 2 expression in superantigen shock. Crit. Care Med. 2008, 36, 1267-1276.
34. Papageorgiou, A.C.; Acharya, K.R. Microbial superantigens: From structure to function. Trends Microbiol. 2000, 8, 369-375.
35. Monday, S.R.; Bohach, G.A. Properties of Staphylococcus aureus Enterotoxins and Toxic Shock Syndrome Toxin-1. In The Comprehensive Sourcebook of Bacterial Protein Toxins; Alouf, J.E., Freer, J.H., Eds.; Academic: London, UK, 1999; pp. 589-610.
36. Wang, X.; Xu, M.; Cai, Y.; Yang, H.; Zhang, H.; Zhang, C. Functional analysis of the disulphide loop mutant of staphylococcal enterotoxin C2. Appl. Microbiol. Biotechnol. 2009, 82, 861-871.
37. Bavari, S.; Ulrich, R.G.; LeClaire, R.D. Cross-reactive antibodies prevent the lethal effects of Staphylococcus aureus superantigens. J. Infect. Dis. 1999, 180, 1365-1369.
38. Kappler, J.W.; Herman, A.; Clements, J.; Marrack, P. Mutations defining functional regions of the superantigen staphylococcal enterotoxin B. J. Exp. Med. 1992, 175, 387-396.
39. Li, H.; Llera, A.; Tsuchiya, D.; Leder, L.; Ysern, X.; Schlievert, P.M.; Karjalainen, K.; Mariuzza, R.A. Three-dimensional structure of the complex between a T cell receptor beta chain and the superantigen staphylococcal enterotoxin B. Immunity 1998, 9, 807-816.
40. Mollick, J.A.; Chintagumpala, M.; Cook, R.G.; Rich, R.R. Staphylococcal exotoxin activation of T cells. Role of exotoxin-MHC class II binding affinity and class II isotype. J. Immunol. 1991, 146, 463-468.
41. Chintagumpala, M.M.; Mollick, J.A.; Rich, R.R. Staphylococcal toxins bind to different sites on HLA-DR. J. Immunol. 1991, 147, 3876-3882.
42. Ulrich, R.G.; Bavari, B.; Olson, M.A. Staphylococcal enterotoxins A and B share a common structural motif for binding class II major histocompatibility complex molecules. Nat. Struct. Biol.1995, 2, 554-560.
43. Hudson, K.R.; Tiedemann, R.E.; Urban, R.G.; Lowe, S.C.; Strominger, J.L.; Fraser, J.D. Staphylococcal enterotoxin A has two cooperative binding sites on major histocompatibility complex class II. J. Exp. Med. 1995, 182, 711-720.
44. Tiedemann, R.E.; Urban, R.J.; Strominger, J.L.; Fraser, J.D. Isolation of HLA-DR1. (staphylococcal enterotoxins A) 2 trimers in solution. Proc. Natl. Acad. Sci. USA 1995, 92, 12156-12159.
45. Thibodeau, J.; Cloutier, I.; Lavoie, P.M.; Labrecque, N.; Mourad, W.; Jardetzky, T.; Sekaly, R.P. Subsets of HLA-DR1 molecules defined by SEB and TSST-1 binding. Science 1994, 266, 1874-1878.
46. Herrmann, T.; Acolla, R.S.; MacDonald, H.R. Different staphylococcal enterotoxins bind preferentially to distinct MHC class II isotypes. Eur. J. Immunol. 1989, 19, 2171-2174.
47. Herman, A.; Croteau, G.; Sekaly, R.P.; Kappler, J.; Marrack, P. HLA-DR alleles differ in their ability to present staphylococcal enterotoxins to T cells. J. Exp. Med. 1990, 172, 709-712.
48. Scholl, P.; Sekaly, R.; Diez, A.; Glimcher, L.; Geha, R. Binding of toxic shock syndrome toxin-1 to murine major histocompatibility complex class II molecules. Eur. J. Immunol. 1990, 20, 1911-1916.
49. Seth, A.; Stern, L.J.; Ottenhoff, T.H.; Engel, I.; Owen, M.J.; Lamb, J.R.; Klausner, R.D.; Wiley, D.C. Binary and ternary complexes between T-cell receptor, class II MHC and superantigen in vitro. Nature 1994, 369, 324-27.
50. Moza, B.; Varma, A.K.; Buonpane, R.A.; Zhu, P.; Herfst, C.A.; Nicholson, M.J.; Wilbuer, A.K.; Seth, N.P.; Wucherpfennig, K.W.; McCormick, J.K.; Kranz, D.M.; Sundberg, E.J. Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1. EMBO J. 2007, 26, 1187-1197.
51. Ferry, T.; Thomas, D.; Perpoint, T.; Lina, G.; Monneret, G.; Mohammedi, I.; Chidiac, C.; Peyramond, D.; Vandenesch, F.; Etienne, J. Analysis of superantigenic toxin Vbeta T-cell signatures produced during cases of staphylococcal toxic shock syndrome and septic shock. Clin. Microbiol. Infect. 2008, 14, 546-554.
52. Arad, G.; Levy, R.; Nasie, I.; Hillman, D.; Rotfogel, Z.; Barash, U.; Supper, E.; Shpilka, T.; Minis, A.; Kaempfer, R. Binding of superantigen toxins into CD28 homodimer interface is essential for induction of cytokine genes that mediate lethal shock. Plos Biol. 2012, 9, e1001149.
53. Germain, R.N. T-cell signaling: The importance of receptor clustering. Curr. Biol. 1997, 7, R640-R644.
54. Chatila, T.; Geha, R.S. Signal transduction by microbial superantigens via MHC class II molecules. Immunol. Rev. 1993, 131, 43-59.
55. Tiedemann, R.E.; Fraser, J.D. Cross-linking of MHC class II molecules by staphylococcal enterotoxin A is essential for antigen-presenting cell and T cell activation. J. Immunol. 1996, 157, 3958-3966.
56. Carlsson, R.; Fischer, H.; Sjogren, H.O. Binding of staphylococcal enterotoxin A to accessory cells is a requirement for its ability to activate human T cells. J. Immunol. 1998, 140, 2484-2488.
57. Anderson, M.R.; Tary-Lehmann, M. Staphylococcal enterotoxin-B-induced lethal shock in mice is T-cell-dependent, but disease susceptibility is defined by the non-T-cell compartment. Clin. Immunol. 2001, 98, 85-94.
58. Fleischer, B.; Schrezenmeier, H. T cell stimulation by staphylococcal enterotoxins. Clonally variable response and requirement for major histocompatibility complex class II molecules on accessory or target cells. J. Exp. Med. 1988, 167, 1697-1707.
59. Linsley, P.S.; Ledbetter, J.A. The role of the CD28 receptor during T cell responses to antigen. Ann. Rev. Immunol. 1993, 11, 191-212.
60. Krakauer, T. Co-stimulatory receptors for the superantigen staphyloccoccal enterotoxin B on human vascular endothelial cells and T cells. J. Leukco. Biol. 1994, 56, 458-463.
61. Cemerski, S.; Shaw, A. Immune synapses in T-cell activation. Curr. Opin. Immunol. 2006, 18, 298-304.
62. Fraser, J.; Newton, M.; Weiss, A. CD28 and T-cell antigen receptor signal transduction coordinately regulates interleukin 2 gene expression in response to superantigen stimulation. J. Exp. Med. 1992, 175, 1131-1134.
63. Boise, L.H.; Minn, A.J.; Noel, P.J.; June, C.H.; Accavitti, M.A.; Lindsten, T.; Thompson, C.B. CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-xl. Immunity 1995, 3, 87-98.
64. Weiss, A.T. Lymphocyte Activation. In Fundamental Immunology, 4th ed.; Paul, W., Ed.; Lippincott-Raven: Philadelphia, PA, USA, 1998; pp. 411-447.
65. Van Leeuwen, J.E.; Samelson, L.E. T cell-antigen receptor signal transduction. Curr. Opin. Immunol. 1999, 11, 242-248.
66. Smith-Garvin, J.E.; Koretzky, G.A.; Jordan, M.S. T cell activation. Annu. Rev. Immunol. 2009, 27, 591-619.
67. Isakov, N.; Altman, A. PKC-theta-mediated signal delivery from the TCR/CD28 surface receptors. Front. Immunol. 2012, 3, 273-284.
68. DiDonato, J.A.; Mercurio, F.; Karin, M. NFκB and the link between inflammation and cancer. Immunol. Rev. 2012, 246, 379-400.
69. Deane, J.A.; Fruman, D.A. Phosphoinositide 3-kinase: Diverse roles in immune cell activation. Annu. Rev. Immunol. 2004, 22, 563-598.
70. Park, S.G.; Schulze-Luehrman, J.; Hayden, M.S.; Hashimoto, N.; Ogawa, W; Kasuga, M.; Ghosh, S.P. Phosphoinositide-dependent kinase 1 integrates T cell receptor and CD28 co-receptor signaling to effect NFκB induction and T cell activation. Nat. Immunol. 2009, 10, 158-166.
71. Cartwright, N.G.; Kashyap, A.K.; Schaefer, B.C. An active kinase domain is required for retention of PKCθ at the immunological synapse. Mol. Biol. Cell 2011, 22, 3491-3497.
72. Carling, D.; Thornton, C.; Woods, A.; Sanders, M.J. AMP-activated protein kinase: New regulation, new roles? Biochem. J. 2012, 445, 11-27.
73. Chatila, T.; Wood, N.; Parsonnet, J.; Geha, R.S. Toxic shock syndrome toxin-1 induces inositol phospholipid turnover, protein kinase C translocation, and calcium mobilization in human T cells. J. Immunol. 1988, 140, 1250-1255.
74. Scholl, P.R.; Trede, N.; Chatila, T.A.; Geha, R.S. Role of protein tyrosine phosphorylation in monokine induction by the staphylococcal superantigen toxic shock syndrome toxin-1. J. Immunol. 1992, 148, 2237-2241.
75. Bueno, C.; Lemke, C.D.; Criado, G.; Baroja, M.L.; Ferguson, S.S.; Rahman, A.K.; Tsoukas, C.D.; McCormick, J.K.; Madrenas, J. Bacterial superantigens bypass Lck-dependent T cell receptor signaling by activating a Galpha11-dependent, PLC-beta-mediated pathway. Immunity 2006, 25, 67-78.
76. Manning, B.D.; Cantley, L.C. AKT/PBK signaling: Navigating downstream. Cell 2007, 129, 1261-1274.
77. Memmott, R.M.; Dennis, P.A. Akt-dependent and independent mechanisms of mTOR regulation in cancer. Cell. Signal. 2009, 21, 656-664.
78. Ghoreschi, K.; Laurence, A.; O'Shea, J.J. Janus kinases in immune cell signaling. Immunol. Rev. 2009, 228, 273-287.
79. Hulme, M.A.; Wasserfall, C.H.; Atkinson, M.A.; Brusko, T.M. Centrol role for interleukin-2 in type 1 diabetes. Diabetes 2012, 61, 14-22.
80. Thomson, A.W.; Turnquist, H.R.; Raimondi, G. Immunoregulatory functions of mTOR inhibition. Nat. Rev. Immunol. 2009, 9, 324-337.
81. Huang, J.; Manning, B.D. A complex interplay between Akt, TSC2 and the two mTOR complexes. Biochem. Soc. Trans. 2009, 37, 217-222.
82. Laplante, M.; Sabatini, D.M. mTOR signaling at a glance. J. cell. Sci. 2009, 122, 3389-3394.
83. Abraham, R.T.; Wiederrecht, O.J. Immunopharmacology of rapamycin. Ann. Rev. Immunol. 1996, 14, 483-510.
84. Sarbassov, D.D.; Ali, S.M.; Sengupta, S.; Sheen, J.H.; Hsu, P.P.; Bagley, A.F.; Markhard, A.L.; Sabatini, D.M. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol. Cell 2006, 22, 159-168.
85. Wullschleger, S.; Loewith, R.; Hall, M.N. TOR signaling in growth and metabolism. Cell 2006, 124, 471-484.
86. Yang, O.; Guan, K.L. Expanding mTOR signaling. Cell Res. 2007, 17, 666-681.
87. Krakauer, T.; Buckley, M.; Issaq, H.J.; Fox, S.D. Rapamycin protects mice from staphylococcal enterotoxin B-induced toxic shock and blocks cytokine release in vitro and in vivo. Antimicrob. Agents Chemother. 2010, 54, 1125-1131.
88. Sims, J.E.; Smith, D.E. The IL-1 family: Regulators of immunity. Nat. Rev. Immunol. 2010, 10, 89-102.
89. Takeuchi, O.; Akira, S. Pattern recognition receptors and inflammation. Cell 2010, 140, 805-820.
90. Vallabhapurapu, S.; Karin, M. Regulation and function of NFκB transcription factors in the immune system. Annu. Rev. Immunol. 2009, 27, 693-733.
91. Mele, T.; Madrenas, J. TLR2 signalling: At the crossroads of commensalism, invasive infections and toxic shock syndrome by Staphylococcus aureus. Int. J. Biochem. Cell. Biol. 2010, 42, 1066-1071.
92. Keystone, E.C.; Ware, C.F. Tumor necrosis factor and anti-tumor necrosis factor therapies. J. Rheumatol. 2010, 85, 27-39.
93. Dunn, G.P.; Koebel, C.M.; Schreiber, R.D. Interferons, immunity and cancer immunoediting. Nat. Rev. Immunol. 2006, 6, 836-848.
94. Murray, P.J. The JAK-STAT signaling pathway: Input and output integration. J. Immunol. 2007, 178, 2623.
95. Ramana, C.V.; Gil, M.P.; Schreiber, R.D.; Stark, G.R. Stat-1-dependent and-independent pathways in IFN-dependent signaling. Trends Immunol. 2002, 23, 96-101.
96. Lu, J.; Philpott, D.J.; Saunders, P.R.; Perdue, M.H.; Yang, P.C.; McKay, D.M. Epithelial ion transport and barrier abnormalities evoked by superantigen-activated immune cells are inhibited by interleukin-10 but not interleukin-4. J. Pharmacol. Exp. Ther. 1998, 287, 128-136.
97. Matthys, P.; Mitera, T.; Heremans, H.; van Damme, J.; Billiau, A. Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice. Infect. Immun. 1995, 63, 1158-1164.
98. Malek, T.R.; Castro, I. Interleukin-2 receptor signaling: At the interface between tolerance and immunity. Immunity 2010, 33, 153-165.
99. Liu, D.; Zienkiewicz, J.; DiGiandomenico, A.; Hawiger, J. Suppression of acute lung inflammation by intracellular peptide delivery of a nuclear import inhibitor. Mol. Ther. 2009, 17, 796-802.
100. Huzella, L.M.; Buckley, M.J.; Alves, D.A.; Stiles, B.G.; Krakauer, T. Central roles for IL-2 and MCP-1 following intranasal exposure to SEB: A new mouse model. Vet. Res. Sci. 2009, 86, 241-247.
101. Khan, A.A.; Priya, S.; Saha, B. IL-2 regulates SEB induced toxic shock syndrome in BALB/c mice. PLoS One 2009, 4, e8473.
102. Wang, X.; Lupardus, P.; LaPorte, S.L.; Garcia, K.C. Structural biology of shared cytokine receptors. Annu. Rev. Immunol. 2009, 27, 27-60.
103. Sadik, C.D.; Kim, N.D.; Luster, A.D. Neutrophils cascading their way to inflammation. Trends Immunol. 2011, 32, 452-460.
104. Zlotnik, A.; Yoshie, D. The chemokine superfamily revisited. Immunity 2012, 36, 705-716.
105. Krakauer, T.; Buckley, M.; Huzella, L.M.; Alves, D. Critical timing, location and duration of glucocorticoid administration rescues mice from superantigen-induced shock and attenuates lung injury. Int. Immunopharmacol. 2009, 9, 1168-1174.
106. Darenberg, J.; Soderquist, B.; Normark, B.H.; Norrby-Teglund, A. Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: Implications for therapy of toxic shock syndrome. Clin. Infect. Dis. 2004, 38, 836-842
107. Tilahun, M.E.; Rajagopalan, G.; Shah-Mahoney, N.; Lawlor, R.G.; Tilahun, A.Y.; Xie, C.; Natarajan, K.; Margulies, D.H.; Ratner, D.I.; Osborne, B.A.; Goldsby, R.A. Potent neutralization of staphylococcal enterotoxin B by synergistic action of chimeric antibodies. Infect. Immun. 2010, 78, 2801-2811.
108. Larkin, E.A.; Stiles, B.G.; Ulrich, R.G. Inhibition of toxic shock by human monoclonal antibodies against staphylococcal enterotoxin B. PLoS One 2010, 5, e13253.
109. Varshney, A.K.; Wang, X.; Cook, E.; Dutta, K.; Scharff, M.D.; Goger, M.J.; Fries, B.C.; Generation, characterization, and epitope mapping of neutralizing and protective monoclonal antibodies against staphylococcal enterotoxin B-induced lethal shock. J. Biol. Chem. 2011, 286, 9737-9747.
110. Bavari, S.; Dyas, B.; Ulrich, R.G. Superantigen vaccines: A comparative study of genetically attenuated receptor-binding mutants of staphylococcal enterotoxin A. J. Infect. Dis. 1996, 174, 338-345.
111. Grumann, D.; Ruotsalainen, E.; Kolata, J.; Kuusela, P.; Jarvinen, A.; Kontinen, V.P.; Broker, B.M.; Holtfreter, S. Characterization of infecting strains and superantigen-neutralizing antibodies in Staphylococcus aureus bacteremia. Clin. Vaccine Immunol. 2001, 18, 487-493.
112. Holtfreter, S.; Roschack, K.; Eichler, P.; Eske, K.; Holtfreter, B.; Kohler, C.; Engelmann, S.; Hecker, M.; Greinacher, A.; Broker, B.M. Staphylococcus aureus carriers neutralize superantigens by antibodies specific for their colonizing strain: A potential explanation for their improved prognosis in severe sepsis. J. Infect. Dis. 2006, 193, 1275-1278.
113. Arad, G.; Levy, R.; Hillman, D.; Kaempfer, R. Superantigen antagonist protects against lethal shock and defines a new domain for T-cell activation. Nat. Med. 2000, 6, 414-421.
114. Visvanathan, K.; Charles, A.; Bannan, J.; Pugach, P.; Kashfi, K.; Zabriskie, J.B. Inhibition of bacterial superantigens by peptides and antibodies. Infect. Immun. 2001, 69, 875-884.
115. Rajagopalan, G.; Sen, M.M.; David, C.S. In vitro and in vivo evaluation of staphylococcal superantigen peptide antagonists. Infect. Immun. 2004, 72, 6733-6737.
116. Geller-Hong, E.; Möllhoff, M.; Shiflett, P.R.; Gupta, G. Design of chimeric receptor mimics with different TcRVβ isoforms: Type-specific inhibition of superantigen pathogenesis. J. Biol. Chem. 2004, 279, 5676-5684.
117. Wang, N.; Mattis, D.M.; Sundberg, E.J.; Schlievert, P.M.; Kranz, D.M. A single, engineered protein therapeutic agent neutralizes exotoxins from both Staphylococcus aureus and Streptococcus pyogenes. Clin. Vacc. Immunol. 2010, 17, 1781-1789.
118. Saha, B.; Jaklic, B.; Harlan, D.M.; Gray, G.S.; June, C.H.; Abe, R. Toxic shock syndrome toxin-1 induced death is prevented by CTLA4Ig. J. Immunol. 1996, 157, 3869-3875.
119. DeGrasse, J.A. A single-stranded DNA apttamer that selectively binds to Staphhylococcus aureeus enterotoxin B. PLos One 2012, 7, e33410.
120. Tak, P.P.; Firestein, G.S. NF-κb, a key role in inflammatory diseases. J. Clin. Invest. 2001, 107, 7-11.
121. Liu, D.; Liu, X.Y.; Robinson, D.; Burnett, C.; Jackson, C.; Seele, L.; Veach, R.A.; Downs, S.; Collins, R.D.; Ballard, R.W.; Hawiger, J. Suppression of staphylococcal enterotoxin B-induced toxicity by a nuclear import inhibitor. J. Biol. Chem. 2004, 279, 19239-19246.
122. Sprung, C.L.; Goodman, S.; Weiss, Y.G. Steriod therapy of septic shock. Crit. Care Clin. 2009, 25, 825-834.
123. Krakauer, T. Differential inhibitory effects of interleukin-10, interleukin-4, and dexamethasone on staphylococcal enterotoxin-induced cytokine production and T cell activation. J. Leukoc. Biol. 1995, 57, 450-454.
124. Krakauer, T.; Buckley, M. Dexamethasone attenuates staphylococcal enterotoxin B-induced hypothermic response and protects mice from superantigen-induced toxic shock. Antimicrob. Agents Chemother. 2006, 50, 391-395.
125. Tilahun, A.Y.; Theuer, J.E.; Patel, R.; David, C.S.; Rajagopalan, G. Detrimental effect of the proteasome inhibitor, bortezomib in bacterial superantigen-and lipopolysaccharide-induced systemic inflammation. Mol. Ther. 2010, 18, 1143-1154.
126. Krakauer, T. Comparative potency of green tea and red wine polyphenols in attenuating staphylococcal superantigen-induced immune responses. Am. J. Biomed. Sci. 2012, doi:10,5099/aj120200157.
127. Watson, J.L.; Vicario, M.; Wang, A.; Moreto, M.; McKay, D.M. Immune cell activation and subsequent epithelial dysfunction by staphylococcal enterotoxin B is attenuated by the green tea polyphenol (-)-epigallocatechin gallate. Cell. Immunol. 2005, 237, 7-16.
128. Rieder, S.A.; Nagarkatti, P.; Nagarkatti, M. Identification of multiple anti-inflammatory pathways triggered by resveratrol leading to amelioration of staphylococcal enterotoxin B-induced lung inflammation. Brit. J. Pharmacol. 2012, 167, 1244-1258.
129. Kissner, T.L.; Ruthel, G.; Alam, S.; Mann, E.; Ajami, D.; Rebek, M.; Larkin, E.; Fernandez, S.; Ulrich, R.G.; Ping, S.; et al. Therapeutic inhibition of pro-inflammatory signaling and toxicity to Staphylococcal enterotoxin B by a synthetic dimeric BB-loop mimetic of MyD88. PLos One 2012, 7, e40773.
130. Kissner, T.L.; Moisan, L.; Mann, E.; Alam, S.; Ruthel, G.; Ulrich, R.G.; Rebek, M.; Rebek, J., Jr.; Saikh, K.U. A small molecule that mimics the BB-loop in the Toll interleukin-1 (IL-1) receptor domain of MyD88 attenuates staphylococcal enterotoxin B-induced pro-inflammatory cytokine production and toxicity in mice. J. Biol. Chem. 2011, 286, 31385-31396.
131. See, R.H.; Chow, A.W. Staphylococcal toxic shock syndrome toxin 1-induced tumor necrosis factor alpha and interleukin-1β secretion by human peripheral blood monocytes and T lymphocytes is differentially suppressed by protein kinase inhibitors. Infect. Immun. 1992, 60, 3456-3459.
132. Krakauer, T. Suppression of endotoxin-and staphylococcal exotoxin-induced cytokines and chemokines by a phospholipase C inhibitor in human peripheral blood mononuclear cells. Clin. Diagn. Lab. Immunol. 2001, 8, 449-453.
133. Tschaikowsky, K.J.; Schmidt, J.; Meisner, M. Modulation of mouse endotoxin shock by inhibition of phosphatidylcholine-specific phospholipase C. J. Pharmacol. Exp. Therap. 1999, 285, 800-804.
134. Jo, D.; Liu, D.; Yao, S.; Collins, R.D.; Hawiger, J. Intracellular protein therapy with SOCS3 inhibits inflammation and apoptosis. Nat. Med. 2005, 11, 892-898.
135. Komisar, J.L.; Weng, C.F.; Oyejide, A.; Hunt, R.E.; Briscoe, C.; Tseng, J. Cellular and cytokine responses in the circulation and tissue reactionsin the lung of rhesus monkeys (Macaca mulatta) pretreated with cyclosporine A and challenged with staphylococcal enterotoxin B. Toxicol. Pathol. 2001, 29, 369.
136. Tilahun, A.Y.; Karau, M.J.; Clark, C.R.; Patel, R.; Rajagopalan, G. The impact of tacrolimus on the immunopathogenesis of with staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia. Microbes Infect. 2012, 14, 528-536.
137. Krakauer, T.; Buckley, B. Intranasal rapamycin rescues mice from staphylococcal enterotoxin-induced shock. Toxins 2012, 4, 718-728.
138. Krakauer, T.; Buckley, M. The potency of anti-oxidants in attenuating superantigen-induced proinflammatory cytokines correlates with inactivation of NFκB. Immunopharmacol. Immunotoxic. 2008, 30, 163-179.
139. Bean, A.G.; Freiberg, R.A.; Andrade, S.; Menon, S.; Zlotnik, A. Interleukin 10 protects mice against staphylococcal enterotoxin B-induced lethal shock. Infect. Immun. 1993, 61, 4937-4939.
140. Florquin, S.; Amraoui, Z.; Abramowicz, D.; Goldman, M. Systemic release and protective role of IL-10 in staphylococcal enterotoxin B-induced shock in mice. J. Immunol. 1994, 153, 2618-2623.
141. LeClaire, R.D.; Kell, W.; Bavari, S.; Smith, T.; Hunt, R.E. Protective effects of niacinamide in staphylococcal enterotoxin B induced toxicity. Toxicology 1996, 107, 69-81.
142. Krakauer, T.; Buckley, M. Doxycycline is anti-inflammatory and inhibits staphylococcal exotoxin-induced cytokines and chemokines. Antimicrob. Agents Chemother. 2003, 47, 3630-3633.
143. Krakauer, T.; Stiles, B.G. Pentoxifylline inhibits staphylococcal superantigen induced toxic shock and cytokine release. Clin. Diagn. Lab. Immunol. 1999, 6, 594-598.
144. Krakauer, T. Caspase inhibitors attenuate superantigen-induced inflammatory cytokines, chemokines and T-cell proliferation. Clin. Diagn. Lab. Immunol. 2004, 11, 621-624.
145. Takei, Y.; Kunikata, T.; Aga, M.; Inoue, S.; Ushio, S.; Iwaki, K.; Ikeda, M.; Kurimoto, M. Tryptanthrin inhibits interferon-γ production by Peyer's patch lymphocytes derived from mice that had been orally administered staphylococcal enterotoxin. Biol. Pharm. Bull. 2003, 26, 365-367.
146. Krakauer, T.; Li, B.; Young, H. The flavonoid baicalin inhibits staphylococcal superantigen-induced inflammatory cytokine and chemokine production in human peripheral blood mononuclear cells. FEBS Lett. 2001, 500, 50-55.