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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. GC70170 Zilucoplan Zilucoplan  Chemical Structure
  3. GC70154 Yakuchinone A Yakuchinone A  Chemical Structure
  4. GC70120 Vixarelimab Vixarelimab  Chemical Structure
  5. GC70119 Vipoglanstat Vipoglanstat  Chemical Structure
  6. GC70116 Vesencumab Vesencumab  Chemical Structure
  7. GC70045 Tozorakimab Tozorakimab  Chemical Structure
  8. GC70026 Thymidine 3',5'-diphosphate tetrasodium Thymidine 3',5'-diphosphate tetrasodium  Chemical Structure
  9. GC70017 Tesidolumab Tesidolumab  Chemical Structure
  10. GC70004 Tebentafusp Tebentafusp  Chemical Structure
  11. GC69998 TBK1-IN-1 TBK1-IN-1  Chemical Structure
  12. GC69963 STING agonist-8 dihydrochloride STING agonist-8 dihydrochloride  Chemical Structure
  13. GC69962 STING agonist-3 trihydrochloride STING agonist-3 trihydrochloride  Chemical Structure
  14. GC69961 STING agonist-22 STING agonist-22  Chemical Structure
  15. GC69959 STING agonist-20 STING agonist-20  Chemical Structure
  16. GC69943 SRI-42127 SRI-42127  Chemical Structure
  17. GC69937 Spesolimab Spesolimab  Chemical Structure
  18. GC69912 SLC7A11-IN-1 SLC7A11-IN-1  Chemical Structure
  19. GC69908 Skatole-d3 Skatole-d3  Chemical Structure
  20. GC69899 SIRT6 activator 12q SIRT6 activator 12q  Chemical Structure
  21. GC69889 Sifalimumab Sifalimumab  Chemical Structure
  22. GC69841 Rubropunctatin Rubropunctatin  Chemical Structure
  23. GC69831 ROS-ERS inducer 1 ROS-ERS inducer 1  Chemical Structure
  24. GC69828 Rolinsatamab Rolinsatamab  Chemical Structure
  25. GC69823 (R)-(-)-Ibuprofen-d3 (R)-(-)-Ibuprofen-d3  Chemical Structure
  26. GC69818 Risankizumab Risankizumab  Chemical Structure
  27. GC69803 Ravulizumab Ravulizumab  Chemical Structure
  28. GC69799 (Rac)-ZLc-002 (Rac)-ZLc-002  Chemical Structure
  29. GC69713 Pivekimab Pivekimab  Chemical Structure
  30. GC69705 Physalin A Physalin A  Chemical Structure
  31. GC69684 Pelecopan Pelecopan  Chemical Structure
  32. GC69641 Oxelumab Oxelumab  Chemical Structure
  33. GC69631 Ordesekimab Ordesekimab  Chemical Structure
  34. GC69621 Olokizumab Olokizumab  Chemical Structure
  35. GC69615 ODN D-SL03 ODN D-SL03  Chemical Structure
  36. GC69613 ODN 6016 ODN 6016  Chemical Structure
  37. GC69595 NSC61610 NSC61610  Chemical Structure
  38. GC69592 NRP1 antagonist 1 NRP1 antagonist 1  Chemical Structure
  39. GC69590 Nrf2 activator-2 Nrf2 activator-2  Chemical Structure
  40. GC69582 ARC186 ARC186  Chemical Structure
  41. GC69573 NLRP3-IN-18 NLRP3-IN-18  Chemical Structure
  42. GC69572 NLRP3-IN-13 NLRP3-IN-13  Chemical Structure
  43. GC69571 NLRP3-IN-11 NLRP3-IN-11  Chemical Structure
  44. GC69570 NLRP3-IN-10 NLRP3-IN-10  Chemical Structure
  45. GC69569 NLRP3/AIM2-IN-2 NLRP3/AIM2-IN-2  Chemical Structure
  46. GC69561 Nidanilimab Nidanilimab  Chemical Structure
  47. GC69556 NF-κB/MAPK-IN-1 NF-κB/MAPK-IN-1  Chemical Structure
  48. GC69555 NF-κB-IN-4 NF-κB-IN-4  Chemical Structure
  49. GC69539 Nasunin Nasunin  Chemical Structure
  50. GC69534 Nadunolimab Nadunolimab  Chemical Structure
  51. GC69530 N-Acetyldopamine dimer-2 N-Acetyldopamine dimer-2  Chemical Structure
  52. GN10814 Quercitrin Quercitrin  Chemical Structure
  53. GN10805 Protopanaxdiol Protopanaxdiol  Chemical Structure
  54. GN10804 Isovitexin Isovitexin  Chemical Structure
  55. GN10799 Ginsenoside Rg3 Ginsenoside Rg3  Chemical Structure
  56. GN10784 Rhoifolin Rhoifolin  Chemical Structure
  57. GN10778 Picroside II Picroside II  Chemical Structure
  58. GN10759 Sanggenone C Sanggenone C  Chemical Structure
  59. GN10741 Garcinone D Garcinone D  Chemical Structure
  60. GN10737 Tanshinone IIA Tanshinone IIA  Chemical Structure
  61. GN10727 Forsythoside B Forsythoside B  Chemical Structure
  62. GN10718 Andrographolide Andrographolide  Chemical Structure
  63. GN10706 Diosimin Diosimin  Chemical Structure
  64. GN10698 Cynarin Cynarin  Chemical Structure
  65. GN10693 Rutin Rutin  Chemical Structure
  66. GN10685 Anemarsaponin B Anemarsaponin B  Chemical Structure
  67. GN10669 Glucosamine sulfate Glucosamine sulfate  Chemical Structure
  68. GN10668 Coenzyme Q10 Coenzyme Q10  Chemical Structure
  69. GN10664 Honokiol Honokiol  Chemical Structure
  70. GN10662 Cichoric Acid Cichoric Acid  Chemical Structure
  71. GN10650 Ziyuglycoside II Ziyuglycoside II  Chemical Structure
  72. GN10646 Engeletin Engeletin  Chemical Structure
  73. GN10627 Atractylenolide I Atractylenolide I  Chemical Structure
  74. GN10614 Ginsenoside Rg2 Ginsenoside Rg2  Chemical Structure
  75. GN10613 Hesperidin Hesperidin  Chemical Structure
  76. GN10599 Procyanidin B2 Procyanidin B2  Chemical Structure
  77. GN10584 Ginsenoside Rk1 Ginsenoside Rk1  Chemical Structure
  78. GN10582 Liquiritin Liquiritin  Chemical Structure
  79. GN10579 Aristolochic Acid A Aristolochic Acid A  Chemical Structure
  80. GN10569 Lobetyolin Lobetyolin  Chemical Structure
  81. GN10550 Neosperidin dihydrochalcone Neosperidin dihydrochalcone  Chemical Structure
  82. GN10549 Ginsenoside Rd Ginsenoside Rd  Chemical Structure
  83. GN10544 Ginsenoside Rg1 Ginsenoside Rg1  Chemical Structure
  84. GN10538 Ginsenoside Rh1 Ginsenoside Rh1  Chemical Structure
  85. GN10536 Aconine Aconine  Chemical Structure
  86. GN10534 Asiaticoside Asiaticoside  Chemical Structure
  87. GN10523 Berberine Sulfate Berberine Sulfate  Chemical Structure
  88. GN10519 Ethyl ferulate Ethyl ferulate  Chemical Structure
  89. GN10518 Chitosamine hydrochloride Chitosamine hydrochloride  Chemical Structure
  90. GN10509 Apigenin-7-O-β-D-glucopyranoside Apigenin-7-O-β-D-glucopyranoside  Chemical Structure
  91. GN10504 Echinocystic acid Echinocystic acid  Chemical Structure
  92. GN10503 Piceatannol Piceatannol  Chemical Structure
  93. GN10491 Mangiferin Mangiferin  Chemical Structure
  94. GN10484 Amentoflavone Amentoflavone  Chemical Structure
  95. GN10475 Rhein Rhein  Chemical Structure
  96. GN10450 Ginsenoside F3 Ginsenoside F3  Chemical Structure
  97. GN10448 Lycopene Lycopene  Chemical Structure
  98. GN10443 Berbamine Berbamine  Chemical Structure
  99. GN10442 Curculigoside Curculigoside  Chemical Structure
  100. GN10436 Morusin Morusin  Chemical Structure
  101. GN10429 Neochlorogenic acid Neochlorogenic acid  Chemical Structure

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