Myeloid Differentiation Factor 88 Is The Bottle Neck of TLR Signaling Pathway_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Lie ^1,2 , LI Yuan ^2,3 ,  ZHOU Zongguang ^1,2

1.Department of Gastrointestinal Surgery， West China Hospital， Sichuan University， Chengdu 610041， Sichuan Province， China;;
2.Laboratory of Digestive Surgery， West China Hospital， Sichuan University， Chengdu 610041， Sichuan Province， China;;
3.Department of Pediatric Surgery， West China Hospital， Sichuan University， Chengdu 610041， Sichuan Province， China;

Corresponding author：

ZHOU Zongguang, Email: zhou767@163.com

Keywords：

Myeloid differentiation factor 88; Toll like receptor; Signaling pathway; Adapter protein; Application value

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To summarize the important role of myeloid differentiation factor 88 （MyD88） in toll like receptor （TLR） signaling pathway， and to summarize the relationship between MyD88 and relative diseases， and its potential application value.
Methods 　Domestic and international publications online involving the role of MyD88 in TLR signaling pathway and the influence of MyD88 in some kinds of diseases in recent years were collected and reviewed.
Results 　MyD88 was an important adapter protein， and played a connecting role in the TLR signaling pathway. It was the bottle neck of TLR signaling pathway， and could lead to the activation of many transcription factor to initiate innate immune response. It was also related to a variety of diseases.
Conclusions 　MyD88 is the key adapter protein in TLR signaling pathway. It plays an important role in innate immunity， acquired immunity， and a variety of diseases， so it is a potential therapeutic target.

Citation： ZHANG Lie,LI Yuan,ZHOU Zongguang. Myeloid Differentiation Factor 88 Is The Bottle Neck of TLR Signaling Pathway. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(6): 685-690. doi: Copy

1.	Arancibia SA， Beltrán CJ， Aguirre IM， et al. Toll-like receptors are key participants in innate immune responses[J]. Biol Res， 2007， 40(2)：97-112.
2.	Sheedy FJ， O’neill LA. The troll in toll：mal and tram as bridges for TLR2 and TLR4 signaling[J]. J Leukoc Biol， 2007， 82(2)：196-203.
3.	方丽娟，孟民杰. 髓样分化因子88研究进展[J]. 广东药学院学报， 2011， 27(2)：215-217.
4.	Li X， Qin J. Modulation of toll-interleukin 1 receptor mediated signaling[J]. J Mol Med， 2005， 83(4)：258-266.
5.	Casanova JL， Abel L， Quintana-Murci L. Human TLRs and IL-1Rsin host defense：natural insights from evolutionary， epidemiological，and clinical genetics[J]. Annu Rev Immunol， 2011， 29：447-491.
6.	Boraschi D， Tagliabue A. The interleukin-1 receptor family[J]. Vitam Horm， 2006， 74：229-254.
7.	Brown J， Wang H， Hajishengallis GN， et al. TLR-signaling networks：an integration of adaptor molecules， kinases， and cross-talk[J]. J Dent Res， 2011， 90(4)：417-427.
8.	Mitchell JA， Paul-Clark MJ， Clarke GW， et al. Critical role of toll-like receptors and nucleotide oligomerisation domain in the regulation of health and disease[J]. J Endocrinol， 2007， 193(3)：323-330.
9.	Oda K， Kitano H. A comprehensive map of the toll-like receptor signaling network[J]. Mol Syst Biol， 2006， 2：2006.
10.	Takeuchi O， Akira S. MyD88 as a bottle neck in Toll/IL-1 signaling[J]. Curr Top Microbiol Immunol， 2002， 270：155-167.
11.	production from regulatory CD11b＋/Gr-1high cells suppressesdevelopment of acute cerulein pancreatitis in mice[J]. Immunol Lett， 2012， 148(2)：172-177.
12.	Jin B， Sun T， Yu XH， et al. The effects of TLR activation on T-celldevelopment and differentiation[J]. Clin Dev Immunol， 2012， 2012：836485.
13.	Kawai T， Akira S. TLR signaling[J]. Semin Immunol， 2007， 19(1)：24-32.
14.	An H， Qian C， Cao X. Regulation of toll-like receptor signaling in the innate immunity[J]. Sci China Life Sci， 2010， 53(1)：34-43.
15.	Taniguchi Y， Yoshioka N， Nakata K， et al. Mechanism for maintaining homeostasis in the immune system of the intestine[J]. Anticancer Res， 2009， 29(11)：4855-4860.
16.	Frantz AL， Rogier EW， Weber CR， et al. Targeted deletion ofMyD88 in intestinal epithelial cells results in compromised antibacterial immunity associated with downregulation of polymericimmunoglobulin receptor， mucin-2， and antibacterial peptides[J].Mucosal Immunol， 2012， 5(5)：501-512.
17.	Hoshi N， Schenten D， Nish SA， et al. MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice[J]. Nat Commun， 2012， 3：1120.
18.	Ling HP， Li W， Zhou ML， et al. Expression of intestinal myeloid differentiation primary response protein 88 (MyD88) following experimental traumatic brain injury in a mouse model[J]. J Surg Res， 2013， 179(1)：e227-e234.
19.	Rakoff-Nahoum S， Medzhitov R. Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88[J]. Science， 2007， 317(5834)：124-127.
20.	Li W， Liu HD， You WC， et al. Enhanced cortical expression of myeloid differentiation primary response protein 88(MyD88) inpatients with traumatic brain injury[J]. J Surg Res， 2013， 180 (1)：133-139.
21.	Babcock AA， Toft-Hansen H， Owens T. Signaling through MyD88 regulates leukocyte recruitment after brain injury[J]. J Immunol， 2008， 181(9)：6481-6490.
22.	Mao SS， Hua R， Zhao XP， et al. Exogenous administration of PACAP alleviates traumatic brain injury in rats through a mechanism involving the TLR4/MyD88/NF-κB pathway[J]. J Neurotrauma， 2012， 29(10)：1941-1959.
23.	Braun TP， Grossberg AJ， Veleva-Rotse BO， et al. Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1β[J]. J Neuroinflammation， 2012， 9：229.
24.	Wang X， Stridh L， Li W， et al. Lipopolysaccharide sensitizes neonatal hypoxic-ischemic brain injury in a MyD88-dependent manner[J]. J Immunol， 2009， 183(11)：7471-7477.
25.	Feng Y， Zou L， Zhang M， et al. MyD88 and trif signaling play distinct roles in cardiac dysfunction and mortality during endotoxin shock and polymicrobial sepsis[J]. Anesthesiology， 2011， 115(3)：555-567.
26.	Singh MV， Swaminathan PD， Luczak ED， et al. MyD88 mediatedinflammatory signaling leads to CaMKⅡ oxidation， cardiac hyper-trophy and death after myocardial infarction[J]. J Mol Cell Cardiol，.
27.	Koike Y， Kanai T， Saeki K， et al. MyD88-dependent interleukin-.
28.	Huang X， Yang Y. Targeting the TLR9-MyD88 pathway in the regulation of adaptive immune responses[J]. Expert Opin Ther Targets， 2010， 14(8)：787-796.
29.	Ve T， Gay NJ， Mansell A， et al. Adaptors in toll-like receptor signaling and their potential as therapeutic targets[J]. Curr Drug Targets， 2012， 13(11)：1360-1374.
30.	梁小明，陈昌辉. 髓样分化因子88在Toll样受体信号通路中的作用及临床意义[J]. 实用儿科临床杂志， 2012， 27(15)：1197-1200.
31.	Lucas K， Maes M. Role of the toll like receptor (TLR) radicalcycle in chronic inflammation：possible treatments targeting the TLR4 pathway[J]. Mol Neurobiol， 2013. [Epub ahead of print].
32.	Fekonja O， Avbelj M， Jerala R. Suppression of TLR signaling by targeting TIR domain-containing proteins[J]. Curr Protein Pept Sci， 2012， 13(8)：776-788.
33.	Henderson C， Goldbach-Mansky R. Monogenic IL-1 mediated autoinflammatory and immunodeficiency syndromes：finding the right balance in response to danger signals[J]. Clin Immunol， 2010， 135(2)：210-222.
34.	Zhu J， Mohan C. Toll-like receptor signaling pathways-therapeuticopportunities[J]. Mediators Inflamm， 2010， 2010：781235.
35.	Netea MG， Wijmenga C， O’neill LA. Genetic variation in toll-like receptors and disease susceptibility[J]. Nat Immunol， 2012， 13(6)：535-542.
36.	Zambirinis CP， Miller G. Signaling via MyD88 in the pancreatic tumor microenvironment：a double-edged sword[J]. Oncoimmunology， 2013， 2(1)：e22567.
37.	， 52(5)：1135-1144.

1. Arancibia SA， Beltrán CJ， Aguirre IM， et al. Toll-like receptors are key participants in innate immune responses[J]. Biol Res， 2007， 40(2)：97-112.
2. Sheedy FJ， O’neill LA. The troll in toll：mal and tram as bridges for TLR2 and TLR4 signaling[J]. J Leukoc Biol， 2007， 82(2)：196-203.
3. 方丽娟，孟民杰. 髓样分化因子88研究进展[J]. 广东药学院学报， 2011， 27(2)：215-217.
4. Li X， Qin J. Modulation of toll-interleukin 1 receptor mediated signaling[J]. J Mol Med， 2005， 83(4)：258-266.
5. Casanova JL， Abel L， Quintana-Murci L. Human TLRs and IL-1Rsin host defense：natural insights from evolutionary， epidemiological，and clinical genetics[J]. Annu Rev Immunol， 2011， 29：447-491.
6. Boraschi D， Tagliabue A. The interleukin-1 receptor family[J]. Vitam Horm， 2006， 74：229-254.
7. Brown J， Wang H， Hajishengallis GN， et al. TLR-signaling networks：an integration of adaptor molecules， kinases， and cross-talk[J]. J Dent Res， 2011， 90(4)：417-427.
8. Mitchell JA， Paul-Clark MJ， Clarke GW， et al. Critical role of toll-like receptors and nucleotide oligomerisation domain in the regulation of health and disease[J]. J Endocrinol， 2007， 193(3)：323-330.
9. Oda K， Kitano H. A comprehensive map of the toll-like receptor signaling network[J]. Mol Syst Biol， 2006， 2：2006.
10. Takeuchi O， Akira S. MyD88 as a bottle neck in Toll/IL-1 signaling[J]. Curr Top Microbiol Immunol， 2002， 270：155-167.
11. production from regulatory CD11b＋/Gr-1high cells suppressesdevelopment of acute cerulein pancreatitis in mice[J]. Immunol Lett， 2012， 148(2)：172-177.
12. Jin B， Sun T， Yu XH， et al. The effects of TLR activation on T-celldevelopment and differentiation[J]. Clin Dev Immunol， 2012， 2012：836485.
13. Kawai T， Akira S. TLR signaling[J]. Semin Immunol， 2007， 19(1)：24-32.
14. An H， Qian C， Cao X. Regulation of toll-like receptor signaling in the innate immunity[J]. Sci China Life Sci， 2010， 53(1)：34-43.
15. Taniguchi Y， Yoshioka N， Nakata K， et al. Mechanism for maintaining homeostasis in the immune system of the intestine[J]. Anticancer Res， 2009， 29(11)：4855-4860.
16. Frantz AL， Rogier EW， Weber CR， et al. Targeted deletion ofMyD88 in intestinal epithelial cells results in compromised antibacterial immunity associated with downregulation of polymericimmunoglobulin receptor， mucin-2， and antibacterial peptides[J].Mucosal Immunol， 2012， 5(5)：501-512.
17. Hoshi N， Schenten D， Nish SA， et al. MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice[J]. Nat Commun， 2012， 3：1120.
18. Ling HP， Li W， Zhou ML， et al. Expression of intestinal myeloid differentiation primary response protein 88 (MyD88) following experimental traumatic brain injury in a mouse model[J]. J Surg Res， 2013， 179(1)：e227-e234.
19. Rakoff-Nahoum S， Medzhitov R. Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88[J]. Science， 2007， 317(5834)：124-127.
20. Li W， Liu HD， You WC， et al. Enhanced cortical expression of myeloid differentiation primary response protein 88(MyD88) inpatients with traumatic brain injury[J]. J Surg Res， 2013， 180 (1)：133-139.
21. Babcock AA， Toft-Hansen H， Owens T. Signaling through MyD88 regulates leukocyte recruitment after brain injury[J]. J Immunol， 2008， 181(9)：6481-6490.
22. Mao SS， Hua R， Zhao XP， et al. Exogenous administration of PACAP alleviates traumatic brain injury in rats through a mechanism involving the TLR4/MyD88/NF-κB pathway[J]. J Neurotrauma， 2012， 29(10)：1941-1959.
23. Braun TP， Grossberg AJ， Veleva-Rotse BO， et al. Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1β[J]. J Neuroinflammation， 2012， 9：229.
24. Wang X， Stridh L， Li W， et al. Lipopolysaccharide sensitizes neonatal hypoxic-ischemic brain injury in a MyD88-dependent manner[J]. J Immunol， 2009， 183(11)：7471-7477.
25. Feng Y， Zou L， Zhang M， et al. MyD88 and trif signaling play distinct roles in cardiac dysfunction and mortality during endotoxin shock and polymicrobial sepsis[J]. Anesthesiology， 2011， 115(3)：555-567.
26. Singh MV， Swaminathan PD， Luczak ED， et al. MyD88 mediatedinflammatory signaling leads to CaMKⅡ oxidation， cardiac hyper-trophy and death after myocardial infarction[J]. J Mol Cell Cardiol，.
27. Koike Y， Kanai T， Saeki K， et al. MyD88-dependent interleukin-.
28. Huang X， Yang Y. Targeting the TLR9-MyD88 pathway in the regulation of adaptive immune responses[J]. Expert Opin Ther Targets， 2010， 14(8)：787-796.
29. Ve T， Gay NJ， Mansell A， et al. Adaptors in toll-like receptor signaling and their potential as therapeutic targets[J]. Curr Drug Targets， 2012， 13(11)：1360-1374.
30. 梁小明，陈昌辉. 髓样分化因子88在Toll样受体信号通路中的作用及临床意义[J]. 实用儿科临床杂志， 2012， 27(15)：1197-1200.
31. Lucas K， Maes M. Role of the toll like receptor (TLR) radicalcycle in chronic inflammation：possible treatments targeting the TLR4 pathway[J]. Mol Neurobiol， 2013. [Epub ahead of print].
32. Fekonja O， Avbelj M， Jerala R. Suppression of TLR signaling by targeting TIR domain-containing proteins[J]. Curr Protein Pept Sci， 2012， 13(8)：776-788.
33. Henderson C， Goldbach-Mansky R. Monogenic IL-1 mediated autoinflammatory and immunodeficiency syndromes：finding the right balance in response to danger signals[J]. Clin Immunol， 2010， 135(2)：210-222.
34. Zhu J， Mohan C. Toll-like receptor signaling pathways-therapeuticopportunities[J]. Mediators Inflamm， 2010， 2010：781235.
35. Netea MG， Wijmenga C， O’neill LA. Genetic variation in toll-like receptors and disease susceptibility[J]. Nat Immunol， 2012， 13(6)：535-542.
36. Zambirinis CP， Miller G. Signaling via MyD88 in the pancreatic tumor microenvironment：a double-edged sword[J]. Oncoimmunology， 2013， 2(1)：e22567.
37. ， 52(5)：1135-1144.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Myeloid Differentiation Factor 88 Is The Bottle Neck of TLR Signaling Pathway

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