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Immunology/Inflammation

The immune and inflammation-related pathway including the Toll-like receptors pathway, the B cell receptor signaling pathway, the T cell receptor signaling pathway, etc.

Toll-like receptors (TLRs) play a central role in host cell recognition and responses to microbial pathogens. TLR4 initially recruits TIRAP and MyD88. MyD88 then recruits IRAKs, TRAF6, and the TAK1 complex, leading to early-stage activation of NF-κB and MAP kinases [1]. TLR4 is endocytosed and delivered to intracellular vesicles and forms a complex with TRAM and TRIF, which then recruits TRAF3 and the protein kinases TBK1 and IKKi. TBK1 and IKKi catalyze the phosphorylation of IRF3, leading to the expression of type I IFN [2].

BCR signaling is initiated through ligation of mIg under conditions that induce phosphorylation of the ITAMs in CD79, leading to the activation of Syk. Once Syk is activated, the BCR signal is transmitted via a series of proteins associated with the adaptor protein B-cell linker (Blnk, SLP-65). Blnk binds CD79a via non-ITAM tyrosines and is phosphorylated by Syk. Phospho-Blnk acts as a scaffold for the assembly of the other components, including Bruton’s tyrosine kinase (Btk), Vav 1, and phospholipase C-gamma 2 (PLCγ2) [3]. Following the assembly of the BCR-signalosome, GRB2 binds and activates the Ras-guanine exchange factor SOS, which in turn activates the small GTPase RAS. The original RAS signal is transmitted and amplified through the mitogen-activated protein kinase (MAPK) pathway, which including the serine/threonine-specific protein kinase RAF followed by MEK and extracellular signal related kinases ERK 1 and 2 [4]. After stimulation of BCR, CD19 is phosphorylated by Lyn. Phosphorylated CD19 activates PI3K by binding to the p85 subunit of PI3K and produce phosphatidylinositol-3,4,5-trisphosphate (PIP3) from PIP2, and PIP3 transmits signals downstream [5].

Central process of T cells responding to specific antigens is the binding of the T-cell receptor (TCR) to specific peptides bound to the major histocompatibility complex which expressed on antigen-presenting cells (APCs). Once TCR connected with its ligand, the ζ-chain–associated protein kinase 70 molecules (Zap-70) are recruited to the TCR-CD3 site and activated, resulting in an initiation of several signaling cascades. Once stimulation, Zap-70 forms complexes with several molecules including SLP-76; and a sequential protein kinase cascade is initiated, consisting of MAP kinase kinase kinase (MAP3K), MAP kinase kinase (MAPKK), and MAP kinase (MAPK) [6]. Two MAPK kinases, MKK4 and MKK7, have been reported to be the primary activators of JNK. MKK3, MKK4, and MKK6 are activators of P38 MAP kinase [7]. MAP kinase pathways are major pathways induced by TCR stimulation, and they play a key role in T-cell responses.

Phosphoinositide 3-kinase (PI3K) binds to the cytosolic domain of CD28, leading to conversion of PIP2 to PIP3, activation of PKB (Akt) and phosphoinositide-dependent kinase 1 (PDK1), and subsequent signaling transduction [8].

 

References

[1] Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors[J]. Nature immunology, 2010, 11(5): 373-384.

[2] Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity[J]. Immunity, 2011, 34(5): 637-650.

[3] Packard T A, Cambier J C. B lymphocyte antigen receptor signaling: initiation, amplification, and regulation[J]. F1000Prime Rep, 2013, 5(40.10): 12703.

[4] Zhong Y, Byrd J C, Dubovsky J A. The B-cell receptor pathway: a critical component of healthy and malignant immune biology[C]//Seminars in hematology. WB Saunders, 2014, 51(3): 206-218.

[5] Baba Y, Matsumoto M, Kurosaki T. Calcium signaling in B cells: regulation of cytosolic Ca 2+ increase and its sensor molecules, STIM1 and STIM2[J]. Molecular immunology, 2014, 62(2): 339-343.

[6] Adachi K, Davis M M. T-cell receptor ligation induces distinct signaling pathways in naive vs. antigen-experienced T cells[J]. Proceedings of the National Academy of Sciences, 2011, 108(4): 1549-1554.

[7] Rincón M, Flavell R A, Davis R A. The Jnk and P38 MAP kinase signaling pathways in T cell–mediated immune responses[J]. Free Radical Biology and Medicine, 2000, 28(9): 1328-1337.

[8] Bashour K T, Gondarenko A, Chen H, et al. CD28 and CD3 have complementary roles in T-cell traction forces[J]. Proceedings of the National Academy of Sciences, 2014, 111(6): 2241-2246.

Products for  Immunology/Inflammation

  1. Cat.No. Product Name Information
  2. GN10814 Quercitrin Quercitrin  Chemical Structure
  3. GN10805 Protopanaxdiol Protopanaxdiol  Chemical Structure
  4. GN10804 Isovitexin Isovitexin  Chemical Structure
  5. GN10799 Ginsenoside Rg3 Ginsenoside Rg3  Chemical Structure
  6. GN10784 Rhoifolin Rhoifolin  Chemical Structure
  7. GN10778 Picroside II Picroside II  Chemical Structure
  8. GN10759 Sanggenone C Sanggenone C  Chemical Structure
  9. GN10741 Garcinone D Garcinone D  Chemical Structure
  10. GN10737 Tanshinone IIA Tanshinone IIA  Chemical Structure
  11. GN10727 Forsythoside B Forsythoside B  Chemical Structure
  12. GN10718 Andrographolide Andrographolide  Chemical Structure
  13. GN10706 Diosimin Diosimin  Chemical Structure
  14. GN10698 Cynarin Cynarin  Chemical Structure
  15. GN10693 Rutin Rutin  Chemical Structure
  16. GN10685 Anemarsaponin B Anemarsaponin B  Chemical Structure
  17. GN10669 Glucosamine sulfate Glucosamine sulfate  Chemical Structure
  18. GN10668 Coenzyme Q10 Coenzyme Q10  Chemical Structure
  19. GN10664 Honokiol Honokiol  Chemical Structure
  20. GN10662 Cichoric Acid Cichoric Acid  Chemical Structure
  21. GN10650 Ziyuglycoside II Ziyuglycoside II  Chemical Structure
  22. GN10646 Engeletin Engeletin  Chemical Structure
  23. GN10627 Atractylenolide I Atractylenolide I  Chemical Structure
  24. GN10614 Ginsenoside Rg2 Ginsenoside Rg2  Chemical Structure
  25. GN10613 Hesperidin Hesperidin  Chemical Structure
  26. GN10599 Procyanidin B2 Procyanidin B2  Chemical Structure
  27. GN10584 Ginsenoside Rk1 Ginsenoside Rk1  Chemical Structure
  28. GN10582 Liquiritin Liquiritin  Chemical Structure
  29. GN10579 Aristolochic Acid A Aristolochic Acid A  Chemical Structure
  30. GN10569 Lobetyolin Lobetyolin  Chemical Structure
  31. GN10550 Neosperidin dihydrochalcone Neosperidin dihydrochalcone  Chemical Structure
  32. GN10549 Ginsenoside Rd Ginsenoside Rd  Chemical Structure
  33. GN10544 Ginsenoside Rg1 Ginsenoside Rg1  Chemical Structure
  34. GN10538 Ginsenoside Rh1 Ginsenoside Rh1  Chemical Structure
  35. GN10536 Aconine Aconine  Chemical Structure
  36. GN10534 Asiaticoside Asiaticoside  Chemical Structure
  37. GN10523 Berberine Sulfate Berberine Sulfate  Chemical Structure
  38. GN10519 Ethyl ferulate Ethyl ferulate  Chemical Structure
  39. GN10518 Chitosamine hydrochloride Chitosamine hydrochloride  Chemical Structure
  40. GN10509 Apigenin-7-O-β-D-glucopyranoside Apigenin-7-O-β-D-glucopyranoside  Chemical Structure
  41. GN10504 Echinocystic acid Echinocystic acid  Chemical Structure
  42. GN10503 Piceatannol Piceatannol  Chemical Structure
  43. GN10491 Mangiferin Mangiferin  Chemical Structure
  44. GN10484 Amentoflavone Amentoflavone  Chemical Structure
  45. GN10475 Rhein Rhein  Chemical Structure
  46. GN10450 Ginsenoside F3 Ginsenoside F3  Chemical Structure
  47. GN10448 Lycopene Lycopene  Chemical Structure
  48. GN10443 Berbamine Berbamine  Chemical Structure
  49. GN10442 Curculigoside Curculigoside  Chemical Structure
  50. GN10436 Morusin Morusin  Chemical Structure
  51. GN10429 Neochlorogenic acid Neochlorogenic acid  Chemical Structure
  52. GN10423 Lipoic acid Lipoic acid  Chemical Structure
  53. GN10422 Echinacoside Echinacoside  Chemical Structure
  54. GN10415 Astilbin Astilbin  Chemical Structure
  55. GN10409 cor-nuside cor-nuside  Chemical Structure
  56. GN10395 Prim-O-glucosylcimifugin Prim-O-glucosylcimifugin  Chemical Structure
  57. GN10388 Gallic acid Gallic acid  Chemical Structure
  58. GN10370 Luteolin Luteolin  Chemical Structure
  59. GN10368 Schisantherin A Schisantherin A  Chemical Structure
  60. GN10358 Berbamine hydrochloride Berbamine hydrochloride  Chemical Structure
  61. GN10357 Parthenolide Parthenolide  Chemical Structure
  62. GN10356 Calycosin-7-glucoside Calycosin-7-glucoside  Chemical Structure
  63. GN10348 Proanthocyanidin B1 Proanthocyanidin B1  Chemical Structure
  64. GN10342 Chondroitin sulfate Chondroitin sulfate  Chemical Structure
  65. GN10338 Compound K Compound K  Chemical Structure
  66. GN10337 Tyrosol Tyrosol  Chemical Structure
  67. GN10325 Nobiletin Nobiletin  Chemical Structure
  68. GN10312 Polygalasaponin F Polygalasaponin F  Chemical Structure
  69. GN10308 Chlorogenic acid Chlorogenic acid  Chemical Structure
  70. GN10307 Ginsenoside Re Ginsenoside Re  Chemical Structure
  71. GN10298 Alibiflorin Alibiflorin  Chemical Structure
  72. GN10292 Silibinin Silibinin  Chemical Structure
  73. GN10280 Sinensetin Sinensetin  Chemical Structure
  74. GN10276 Naringenin Naringenin  Chemical Structure
  75. GN10269 Wedelolactone Wedelolactone  Chemical Structure
  76. GN10264 Isochlorogenic acid A Isochlorogenic acid A  Chemical Structure
  77. GN10260 Sarsasapogenin Sarsasapogenin  Chemical Structure
  78. GN10254 Ginsenoside Rc Ginsenoside Rc  Chemical Structure
  79. GN10237 Protopine Protopine  Chemical Structure
  80. GN10221 Berberine Berberine  Chemical Structure
  81. GN10220 Ginsenoside Rb3 Ginsenoside Rb3  Chemical Structure
  82. GN10216 Shikonin Shikonin  Chemical Structure
  83. GN10213 Sinomenine Hydrochloride Sinomenine Hydrochloride  Chemical Structure
  84. GN10212 8-O-Acetyl shanzhiside methyl ester 8-O-Acetyl shanzhiside methyl ester  Chemical Structure
  85. GN10208 Berberine hydrochloride Berberine hydrochloride  Chemical Structure
  86. GN10205 Irisflorentin Irisflorentin  Chemical Structure
  87. GN10185 Rhynchophylline Rhynchophylline  Chemical Structure
  88. GN10178 Cyclohexanecarboxylicacid Cyclohexanecarboxylicacid  Chemical Structure
  89. GN10172 Ruscogenin Ruscogenin  Chemical Structure
  90. GN10164 Saikosaponin D Saikosaponin D  Chemical Structure
  91. GN10156 Ginsenoside Rb1 Ginsenoside Rb1  Chemical Structure
  92. GN10132 Schizandrin B Schizandrin B  Chemical Structure
  93. GN10120 Pinocembrin Pinocembrin  Chemical Structure
  94. GN10119 Zingerone Zingerone  Chemical Structure
  95. GN10118 Desacetyl asperulosidic acid Desacetyl asperulosidic acid  Chemical Structure
  96. GN10103 Neferine Neferine  Chemical Structure
  97. GN10098 Glabridin Glabridin  Chemical Structure
  98. GN10091 Schaftoside Schaftoside  Chemical Structure
  99. GN10074 Xanthotoxol Xanthotoxol  Chemical Structure
  100. GN10056 Dihydroartemisinin Dihydroartemisinin  Chemical Structure
  101. GN10055 Mulberroside A Mulberroside A  Chemical Structure

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