TLR2 ligand induces protection against cerebral ischemia/reperfusion injury via activation of phosphoinositide 3-kinase/Akt signaling

Journal of Immunology

Volumn 187, Issue 3, 2011, Pages 1458-1466

  Lu, Chen ^a,b   Liu, Li ^b   Chen, Yuling ^b   Ha, Tuanzhu ^a   Kelley, Jim ^a   Schweitzer, John ^a   Kalbfleisch, John H ^a   Kao, Race L ^a   Williams, David L ^a   Li, Chuanfu ^a  

^a East Tennessee State University   (United States)

^b NANJING MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 3; GLYCOGEN SYNTHASE KINASE 3BETA; HEAT SHOCK PROTEIN 27; HEAT SHOCK PROTEIN 70; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LIGAND; PAM3CSK4; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BAX; PROTEIN BCL 2; PROTEIN KINASE B; TOLL LIKE RECEPTOR 2; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN BLOOD FLOW; BRAIN INFARCTION SIZE; BRAIN ISCHEMIA; BRAIN NERVE CELL; BRAIN TISSUE; CONTROLLED STUDY; DRUG ACTIVITY; ENZYME INHIBITION; HIPPOCAMPUS; MALE; MICROGLIA; MORPHOLOGY; MOUSE; NERVE CELL LESION; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; REPERFUSION INJURY;

ANIMALS; ENZYME ACTIVATION; INFARCTION, MIDDLE CEREBRAL ARTERY; LIGANDS; LIPOPEPTIDES; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; PHOSPHATIDYLINOSITOL 3-KINASE; PROTO-ONCOGENE PROTEINS C-AKT; REPERFUSION INJURY; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 2;

EID: 80051632188     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1003428     Document Type: Article

References (51)

1. Stoll, G. 2002. Inflammatory cytokines in the nervous system: multifunctional mediators in autoimmunity and cerebral ischemia. Rev. Neurol. (Paris) 158: 887-891. (Pubitemid 35303620)
2. Caso, J. R., J. M. Pradillo, O. Hurtado, P. Lorenzo, M. A. Moro, and I. Lizasoain. 2007. Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation 115: 1599-1608. (Pubitemid 46648645)
3. Tang, S. C., T. V. Arumugam, X. Xu, A. Cheng, M. R. Mughal, D. G. Jo, J. D. Lathia, D. A. Siler, S. Chigurupati, X. Ouyang, et al. 2007. Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proc. Natl. Acad. Sci. USA 104: 13798-13803. (Pubitemid 350003400)
4. Hua, F., J. Ma, T. Ha, Y. Xia, J. Kelley, D. L. Williams, R. L. Kao, I. W. Browder, J. B. Schweitzer, J. H. Kalbfleisch, and C. Li. 2007. Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion. J. Neuroimmunol. 190: 101-111. (Pubitemid 47625617)
5. Hua, F., J. Ma, T. Ha, J. Kelley, D. L. Williams, R. L. Kao, J. H. Kalbfleisch, I. W. Browder, and C. Li. 2008. Preconditioning with a TLR2 specific ligand increases resistance to cerebral ischemia/reperfusion injury. J. Neuroimmunol. 199: 75-82.
6. Hua, F., J. Ma, T. Ha, J. L. Kelley, R. L. Kao, J. B. Schweitzer, J. H. Kalbfleisch, D. L. Williams, and C. Li. 2009. Differential roles of TLR2 and TLR4 in acute focal cerebral ischemia/reperfusion injury in mice. Brain Res. 1262: 100-108.
7. Medzhitov, R., P. Preston-Hurlburt, and C. A. Janeway Jr. 1997. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388: 394-397. (Pubitemid 27334820)
8. Zhang, G., and S. Ghosh. 2001. Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity. J. Clin. Invest. 107: 13-19. (Pubitemid 32047406)
9. Aderem, A., and R. J. Ulevitch. 2000. Toll-like receptors in the induction of the innate immune response. Nature 406: 782-787.
10. Doyle, S. L., and L. A. J. O'Neill. 2006. Toll-like receptors: from the discovery of NFkappaB to new insights into transcriptional regulations in innate immunity. Biochem. Pharmacol. 72: 1102-1113. (Pubitemid 44468394)
11. Porter, A. G., and R. U. Jänicke. 1999. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 6: 99-104. (Pubitemid 29082297)
12. Cao, C. X., Q. W. Yang, F. L. Lv, J. Cui, H. B. Fu, and J. Z. Wang. 2007. Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice. Biochem. Biophys. Res. Commun. 353: 509-514. (Pubitemid 46023466)
13. Lehnardt, S., S. Lehmann, D. Kaul, K. Tschimmel, O. Hoffmann, S. Cho, C. Krueger, R. Nitsch, A. Meisel, and J. R. Weber. 2007. Toll-like receptor 2 mediates CNS injury in focal cerebral ischemia. J. Neuroimmunol. 190: 28-33. (Pubitemid 47625604)
14. Ziegler, G., D. Harhausen, C. Schepers, O. Hoffmann, C. Röhr, V. Prinz, J. König, H. Lehrach, W. Nietfeld, and G. Trendelenburg. 2007. TLR2 has a detrimental role in mouse transient focal cerebral ischemia. Biochem. Biophys. Res. Commun. 359: 574-579. (Pubitemid 46898990)
15. Ha, T., Y. Hu, L. Liu, C. Lu, J. R. McMullen, J. Kelley, R. L. Kao, D. L. Williams, X. Gao, and C. Li. 2010. TLR2 ligands induce cardioprotection against ischaemia/reperfusion injury through a PI3K/Akt-dependent mechanism. Cardiovasc. Res. 87: 694-703.
16. Ha, T., C. Lu, L. Liu, F. Hua, Y. Hu, J. Kelley, K. Singh, R. L. Kao, J. Kalbfleisch, D. L. Williams, et al. 2010. TLR2 ligands attenuate cardiac dysfunction in polymicrobial sepsis via a phosphoinositide 3-kinase-dependent mechanism. Am. J. Physiol. Heart Circ. Physiol. 298: H984-H991.
17. Mersmann, J., R. Berkels, P. Zacharowski, N. Tran, A. Koch, K. Iekushi, S. Dimmeler, T. F. Granja, O. Boehm, W. C. Claycomb, and K. Zacharowski. 2010. Preconditioning by toll-like receptor 2 agonist Pam3CSK4 reduces CXCL1-dependent leukocyte recruitment in murine myocardial ischemia/reperfusion injury. Crit. Care Med. 38: 903-909.
18. Zhao, H., R. M. Sapolsky, and G. K. Steinberg. 2006. Phosphoinositide-3- kinase/akt survival signal pathways are implicated in neuronal survival after stroke. Mol. Neurobiol. 34: 249-270.
19. Endo, H., C. Nito, H. Kamada, T. Nishi, and P. H. Chan. 2006. Activation of the Akt/GSK3beta signaling pathway mediates survival of vulnerable hippocampal neurons after transient global cerebral ischemia in rats. J. Cereb. Blood Flow Metab. 26: 1479-1489. (Pubitemid 44809077)
20. Arbibe, L., J.-P. Mira, N. Teusch, L. Kline, M. Guha, N. Mackman, P. J. Godowski, R. J. Ulevitch, and U. G. Knaus. 2000. Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway. Nat. Immunol. 1: 533-540.
21. Fukao, T., and S. Koyasu. 2003. PI3K and negative regulation of TLR signaling. Trends Immunol. 24: 358-363. (Pubitemid 36830961)
22. Santos-Sierra, S., S. D. Deshmukh, J. Kalnitski, P. Küenzi, M. P. Wymann, D. T. Golenbock, and P. Henneke. 2009. Mal connects TLR2 to PI3Kinase activation and phagocyte polarization. EMBO J. 28: 2018-2027.
23. Lu, C., F. Hua, L. Liu, T. Ha, J. Kalbfleisch, J. Schweitzer, J. Kelley, R. Kao, D. Williams, and C. Li. 2010. Scavenger receptor class-A has a central role in cerebral ischemia-reperfusion injury. J. Cereb. Blood Flow Metab. 30: 1972-1981.
24. Li, C., T. Ha, J. Kelley, X. Gao, Y. Qiu, R. L. Kao, W. Browder, and D. L. Williams. 2004. Modulating Toll-like receptor mediated signaling by (1→3)-b-D-glucan rapidly induces cardioprotection. Cardiovasc. Res. 61: 538-547. (Pubitemid 38210159)
25. Schneider, A., A. Martin-Villalba, F. Weih, J. Vogel, T. Wirth, and M. Schwaninger. 1999. NF-kappaB is activated and promotes cell death in focal cerebral ischemia. Nat. Med. 5: 554-559. (Pubitemid 29220215)
26. Stetler, R. A., G. Cao, Y. Gao, F. Zhang, S. Wang, Z. Weng, P. Vosler, L. Zhang, A. Signore, S. H. Graham, and J. Chen. 2008. Hsp27 protects against ischemic brain injury via attenuation of a novel stress-response cascade upstream of mitochondrial cell death signaling. J. Neurosci. 28: 13038-13055.
27. Badin, R. A., M. Modo, M. Cheetham, D. L. Thomas, D. G. Gadian, D. S. Latchman, and M. F. Lythgoe. 2009. Protective effect of post-ischaemic viral delivery of heat shock proteins in vivo. J. Cereb. Blood Flow Metab. 29: 254-263.
28. van der Weerd, L., M. F. Lythgoe, R. A. Badin, L. M. Valentim, M. T. Akbar, J. S. de Belleroche, D. S. Latchman, and D. G. Gadian. 2005. Neuroprotective effects of HSP70 overexpression after cerebral ischaemia-an MRI study. Exp. Neurol. 195: 257-266.
29. Chen, Z. C., W. S. Wu, M. T. Lin, and C. C. Hsu. 2009. Protective effect of transgenic expression of porcine heat shock protein 70 on hypothalamic ischemic and oxidative damage in a mouse model of heatstroke. BMC Neurosci. 10: 111.
30. Weinstein, J. R., I. P. Koerner, and T. Möller. 2010. Microglia in ischemic brain injury. Future Neurol 5: 227-246.
31. Hyakkoku, K., J. Hamanaka, K. Tsuruma, M. Shimazawa, H. Tanaka, S. Uematsu, S. Akira, N. Inagaki, H. Nagai, and H. Hara. 2010. Toll-like receptor 4 (TLR4), but not TLR3 or TLR9, knock-out mice have neuroprotective effects against focal cerebral ischemia. Neuroscience 171: 258-267.
32. Hua, F., J. Wang, I. Sayeed, T. Ishrat, F. Atif, and D. G. Stein. 2009. The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice. Biochem. Biophys. Res. Commun. 390: 678-683.
33. Yang, Q. W., J. C. Li, F. L. Lu, A. Q. Wen, J. Xiang, L. L. Zhang, Z. Y. Huang, and J. Z. Wang. 2008. Upregulated expression of toll-like receptor 4 in monocytes correlates with severity of acute cerebral infarction. J. Cereb. Blood Flow Metab. 28: 1588-1596.
34. Marsh, B. J., R. L. Williams-Karnesky, and M. P. Stenzel-Poore. 2009. Toll-like receptor signaling in endogenous neuroprotection and stroke. Neuroscience 158: 1007-1020.
35. Ha, T., F. Hua, X. Liu, J. Ma, J. R. McMullen, T. Shioi, S. Izumo, J. Kelley, X. Gao, W. Browder, et al. 2008. Lipopolysaccharide-induced myocardial protection against ischaemia/reperfusion injury is mediated through a PI3K/Akt-dependent mechanism. Cardiovasc. Res. 78: 546-553. (Pubitemid 351769766)
36. Stevens, S. L., T. M. Ciesielski, B. J. Marsh, T. Yang, D. S. Homen, J. L. Boule, N. S. Lessov, R. P. Simon, and M. P. Stenzel-Poore. 2008. Toll-like receptor 9: a new target of ischemic preconditioning in the brain. J. Cereb. Blood Flow Metab. 28: 1040-1047. (Pubitemid 351589642)
37. Zhang, J. X., H. S. Wu, H. Wang, J. H. Zhang, Y. Wang, and Q. C. Zheng. 2005. Protection against hepatic ischemia/reperfusion injury via downregulation of toll-like receptor 2 expression by inhibition of Kupffer cell function. World J. Gastroenterol. 11: 4423-4426. (Pubitemid 41093966)
38. Leemans, J. C., G. Stokman, N. Claessen, K. M. Rouschop, G. J. Teske, C. J. Kirschning, S. Akira, T. van der Poll, J. J. Weening, and S. Florquin. 2005. Renal-associated TLR2 mediates ischemia/reperfusion injury in the kidney. J. Clin. Invest. 115: 2894-2903. (Pubitemid 41434417)
39. Sakata, Y., J.-W. Dong, J. G. Vallejo, C.-H. Huang, J. S. Baker, K. J. Tracey, O. Tacheuchi, S. Akira, and D. L. Mann. 2007. Toll-like receptor 2 modulates left ventricular function following ischemia-reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 292: H503-H509. (Pubitemid 46105213)
40. Shen, X. D., B. Ke, Y. Zhai, F. Gao, R. W. Busuttil, G. Cheng, and J. W. Kupiec-Weglinski. 2005. Toll-like receptor and heme oxygenase-1 signaling in hepatic ischemia/reperfusion injury. Am. J. Transplant. 5: 1793-1800. (Pubitemid 41039851)
41. Aprahamian, C. J., R. G. Lorenz, C. M. Harmon, and R. A. Dimmit. 2008. Toll-like receptor 2 is protective of ischemia-reperfusion-mediated small-bowel injury in a murine model. Pediatr. Crit. Care Med. 9: 105-109.
42. Abarbanell, A. M., Y. Wang, J. L. Herrmann, B. R. Weil, J. A. Poynter, M. C. Manukyan, and D. R. Meldrum. 2010. Toll-like receptor 2 mediates mesenchymal stem cell-associated myocardial recovery and VEGF production following acute ischemia-reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 298: H1529-H1536.
43. Ziegler, G., D. Freyer, D. Harhausen, U. Khojasteh, W. Nietfeld, and G. Trendelenburg. 2011. Blocking TLR2 in vivo protects against accumulation of inflammatory cells and neuronal injury in experimental stroke. J. Cereb. Blood Flow Metab. 31: 757-766.
44. Fukao, T., M. Tanabe, Y. Terauchi, T. Ota, S. Matsuda, T. Asano, T. Kadowaki, T. Takeuchi, and S. Koyasu. 2002. PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat. Immunol. 3: 875-881.
45. Ojaniemi, M., V. Glumoff, K. Harju, M. Liljeroos, K. Vuori, and M. Hallman. 2003. Phosphatidylinositol 3-kinase is involved in Toll-like receptor 4-mediated cytokine expression in mouse macrophages. Eur. J. Immunol. 33: 597-605. (Pubitemid 36367663)
46. Broughton, B. R. S., D. C. Reutens, and C. G. Sobey. 2009. Apoptotic mechanisms after cerebral ischemia. Stroke 40: e331-e339.
47. Fujio, Y., T. Nguyen, D. Wencker, R. N. Kitsis, and K. Walsh. 2000. Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation 101: 660-667. (Pubitemid 30094738)
48. Liu, L., X. Zhang, B. Qian, X. Min, X. Gao, C. Li, Y. Cheng, and J. Huang. 2007. Over-expression of heat shock protein 27 attenuates doxorubicin-induced cardiac dysfunction in mice. Eur. J. Heart Fail. 9: 762-769. (Pubitemid 47214666)
49. You, W., X. Min, X. Zhang, B. Qian, S. Pang, Z. Ding, C. Li, X. Gao, R. Di, Y. Cheng, and L. Liu. 2009. Cardiac-specific expression of heat shock protein 27 attenuated endotoxin-induced cardiac dysfunction and mortality in mice through a PI3K/Akt-dependent mechanism. Shock 32: 108-117.
50. Zhou, J., T. Schmid, R. Frank, and B. Brüne. 2004. PI3K/Akt is required for heat shock proteins to protect hypoxia-inducible factor 1alpha from pVHL-independent degradation. J. Biol. Chem. 279: 13506-13513. (Pubitemid 38468875)
51. Rafiee, P., M. E. Theriot, V. M. Nelson, J. Heidemann, Y. Kanaa, S. A. Horowitz, A. Rogaczewski, C. P. Johnson, I. Ali, R. Shaker, and D. G. Binion. 2006. Human esophageal microvascular endothelial cells respond to acidic pH stress by PI3K/AKT and p38 MAPK-regulated induction of Hsp70 and Hsp27. Am. J. Physiol. Cell Physiol. 291: C931-C945. (Pubitemid 44771812)