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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. A1072 immunoglobulin light chain variable region fragment [Homo sapiens]/[Mus musculus] Immunoglobulin light chain fragment
  3. A1093 transferrin fragment Transferrin fragment
  4. A1082 ovalbumin (324-338) [Gallus gallus]/[Coturnix coturnix] Triggers immuno response
  5. A1081 MHC class II antigen (45-57) [Homo sapiens] Major histocompatibility complex
  6. A1027 β-Interleukin II (44-56) Cytokine,regulating WBC
  7. A1073 Immunoglobulin M heavy chain (IGHM) fragment [Homo sapiens] Immunoglobulin M heavy chain
  8. A1052 alpha-1 antitrypsin fragment 235-243 [Homo sapiens]/[Papio hamadryas]/[Cercopithecus aethiops] Protease inhibitor
  9. A1071 immunoglobulin light chain variable region fragment [Homo sapiens] Immunoglobulin light chain fragment
  10. A1070 IgG light chain variable region [Homo sapiens]/IgM/kappa antibody [Mus musculus] IgG light chain region
  11. A1069 ferritin heavy chain fragment [Multiple species] Ferritin heavy chain fragment
  12. A1065 egg white lysozyme (19-36) [Gallus gallus] Dissolution of cell wall
  13. A1141 hemagglutinin (332-340) [Influenza A virus] Partial antigenic glycoprotein
  14. A1142 hemagglutinin precursor (114-122) amide [Influenza A virus] Partial antigenic glycoprotein
  15. B5915 Cyclosporin D An immunosuppressive agent
  16. A1024 LEP (116-130) (mouse) An antiobesity hormone
  17. A1121 Melanocyte stimulating hormone release inhibiting factor MSH release-inhibiting factor
  18. A1131 COG 133 ApoE mimetic peptide
  19. A1008 Anti-Inflammatory Peptide 1 PLA2 inhibitor
  20. A1010 Myelopeptide-2 (MP-2) Peptide used for restoring human T lymphocytes
  21. A1025 a-MSH, amide Melanocyte-stimulating hormones
  22. A1026 β-Interleukin I (163-171), human T cell activator
  23. A1030 Interleukin II (60-70) Cytokine,regulating WBC
  24. A1051 alpha-1 antitrypsin fragment Protease inhibitor
  25. A1053 amyloid A protein fragment [Homo sapiens] Apolipoproteins related to HDL in plasma
  26. A2486 Malotilate Stimulates hepatocyte regeneration
  27. A5384 Zileuton 5-lipoxygenase (5-LOX) inhibitor, orally active
  28. B1207 Zileuton sodium 5-lipoxygenase and leukotrienes inhibitor
  29. B3422 U-73122 inhibitor of phospholipase C, phospholipase A2, and 5-LO (5-lipoxygenase)
  30. B5447 BAY-X 1005 Potent FLAP inhibitor
  31. B6391 2-TEDC 5-, 12-, and 15-lipoxygenase inhibitor
  32. B6680 BW-B 70C 5-Lipoxygenase inhibitor,potent and selective
  33. B6684 MK 886 FLAP and PPARα inhibitor, inhibits leukotriene biosynthesis
  34. B7208 PD 146176 15-lipoxygenase (15-LOX) inhibitor
  35. B8014 ML355 12-LOX inhibitor
  36. C4123 β-acetyl-Boswellic Acid non-reducing inhibitor of 5-lipoxygenase (5-LO)
  37. B1187 Imiquimod maleate Immune response modifier
  38. B1054 Resiquimod (R-848) Immune response modifier
  39. B1186 Imiquimod hydrochloride Toll-like receptor 7 agonist
  40. A3850 TAK-242 TLR 4 signaling inhibitor
  41. B2133 Suprofen dual COX-1/COX-2 inhibitor
  42. A3881 Toll-like receptor modulator TLR antagonist
  43. A3851 TAK-242 S enantiomer TLR 4 signaling inhibitor
  44. B5666 Pam2CSK4 Biotin biotinylated Pam2CSK4, a toll-like receptor 2/6 agonist
  45. B5665 Pam2CSK4 toll-like receptor 2/6 (TLR2/6) agonist
  46. B5664 Pam3CSK4 Biotin biotinylated Pam3CSK4, a toll-like receptor 1/2 agonist
  47. B5662 Pam3CSK4 toll-like receptor 1/2 agonist
  48. B5752 CU CPT 4a TLR3 inhibitor
  49. B5753 CU CPT 22 toll-like receptor 1/2 (TLR1/2) inhibitor
  50. B5551 Poly(I:C) Toll-like receptor 3 (TLR3) agonist
  51. B7159 RWJ 21757 Toll-like receptor 7 (TLR7) agonist
  52. A1035 Papain Inhibitor Inhibitor of peptidase activity of Papain
  53. B1046 HPGDS inhibitor 1 HPGDS inhibitor
  54. A8434 Flurbiprofen Cyclooxygenase inhibitors
  55. B1969 Mesalamine IKK inhibitor
  56. B1052 HG-9-91-01 Pan-SIK (salt-inducible kinases) inhibitor
  57. B1643 Sodium 4-Aminosalicylate NF-κB inhibitor
  58. A4217 QNZ (EVP4593) Potent NF-κB inhibitor
  59. A3229 Bay 65-1942 free base IKKβ kinase inhibitor,ATP-competitive
  60. A2604 Celastrol Antioxidant, anti-inflammatory and immunosuppressive agent
  61. A4210 Bay 11-7821(BAY 11-7082) IKK/NF-κB/TNFα inhibitor
  62. A3230 Bay 65-1942 HCl salt IKKβ kinase inhibitor
  63. A3231 Bay 65-1942 R form IKKβ inhibitor, ATP-competitive and selective
  64. B1587 IMD 0354 IKKβ inhibitor
  65. B2028 Sodium salicylate NF-κB inhibitor
  66. B1586 IKK-16 (IKK Inhibitor VII) Selective IκB kinase inhibitor
  67. A4602 TPCA-1 IKK-2 inhibitor,potent and selective
  68. A3486 IKK-3 Inhibitor IKK-3 Inhibitor
  69. A3392 Emodin Naturally occurring anthraquinone,antiproliferative
  70. A3311 CID-2858522 NF-κB pathway inhibitor
  71. A3308 Choline Fenofibrate Choline salt of fenofibric acid
  72. B5543 PF 184 IKKβ inhibitor
  73. B4655 BMS-345541(free base) IKK-1/IKK-2 inhibitor,potent and selective
  74. A3635 MRT67307 SIK/TBK-1/IKKe inhibitor
  75. A3628 MLN120B IκB Kinase β Inhibitor
  76. A3248 BMS345541 hydrochloride IKK inhibitor,highly selective
  77. N2031 Piceatannol p56lck/Syk inhibitor
  78. N2131 Wedelolactone IKK inhibitor
  79. N1855 Andrographolide NF-κB signaling Inhibitor
  80. N1846 Tanshinone IIA Antioxidant and anti-inflammatory reagent
  81. N1831 Luteolin Antioxidant and free radical scavenger
  82. N1672 Honokiol Antioxidant/antitumor/antiangiogenic agent
  83. B5756 ML 120B dihydrochloride IKK2-selective inhibitor
  84. B5638 ACHP IκB kinase inhibitor
  85. B7683 PS 1145 dihydrochloride IκB kinase (IKK) inhibitor
  86. B4880 WS6 inducer of β cell proliferation
  87. B4825 IKKε-IN-1 potent IKKε inhibitor
  88. B4986 LY2409881 potent and selective IKK2 inhibitor
  89. A3485 IKK-2 inhibitor VIII IKK-2 inhibitor,potent and selective
  90. B6089 PS-1145 IKK inhibitor
  91. C4569 IKK-16 (hydrochloride) IκB kinases (IKKs) inhibitor
  92. B1585 SC-514 ATP-competitive IKK-2 inhibitor, orally active
  93. B3033 Bay 11-7085 NK-κB activation inhibitor
  94. A8185 SR 11302 AP-1 transcription factor inhibitor
  95. B7761 AI-3 Nrf2/Keap1 and Keap1/Cul3 interaction inhibitor
  96. B5721 TAT 14 Nrf2 activator
  97. A3335 Curcumin Tyrosinase inhibitor
  98. A3220 Bardoxolone Once-a-day treatment for CKD
  99. B1931 Dimethyl Fumarate nuclear factor (erythroid-derived)-like 2 (Nrf2) pathway activator
  100. N2285 Dimethylfraxetin Extracted from Fraxinus chinensis;Store the product in sealed, cool and dry condition.
  101. C3283 2-Trifluoromethyl-2'-methoxychalcone Nrf2 activator
  102. B1646 ML130 (Nodinitib-1) Potent and selective inhibitor of NOD1
  103. C3427 Polyinosinic-polycytidylic Acid (potassium salt) synthetic dsRNA that activates TLR3 and retinoic acid inducible gene 1 (RIG-1)-like receptors
  104. C5785 Gardiquimod agonist of human toll-like receptor 7 (TLR7)
  105. N1315 Parthenolide Parthenolide is a sesquiterpene lactone and active principle of feverfew (Chrysanthemum parthenium)
  106. A3891 Triptolide IL-2/MMP-3/MMP7/MMP19 inhibitor
  107. A8526 Strontium Ranelate Calcium Channel activator
  108. B1644 Caffeic Acid Phenethyl Ester NF-κB activation inhibitor
  109. B1645 JSH-23 NF-κB inhibitor
  110. C4107 N-3-oxo-dodecanoyl-L-Homoserine lactone NF-κB and AP-2 activator
  111. B6422 Pyrrolidinedithiocarbamate ammonium NF-κB inhibitor
  112. B7199 Withaferin A Prevents NF-κB activation by inhibiting activation of IKKβ
  113. B5241 PR 39 (porcine) Antibacterial peptide
  114. B6853 Ro 106-9920 Inhibitor of NF-κB activation
  115. B7085 Cardamonin NF-κB inhibitor
  116. C3559 NF-κB Activation Inhibitor III NF-κB inhibitor
  117. C4074 PPM-18 NF-κB inhibitor
  118. B4749 SC75741 NF-κB inhibitor, potent
  119. B3425 Y-320 immunomodulator
  120. A3516 JC-1 Probe for Mitochondrial Membrane Potential
  121. B4690 Tyrphostin A1 IL-12 production inhibitor
  122. C3420 Cannabidiol dimethyl ether 15-lipoxygenase inhibitor
  123. C4277 ML351 human reticulocyte 15-LO-1 inhibitor
  124. C4417 Isoprinosine immunomodulatory effects
  125. C4596 ATB-343 hybrid molecule of an H2S donor and the NSAID indomethacin
  126. C4298 (±)-Lisofylline anti-inflammatory agent
  127. C4158 (R)-Lisofylline anti-inflammatory agent
  128. C4161 (S)-Lisofylline inactive optical enantiomer of (R)-LSF, an anti-inflammatory agent
  129. C4126 Bradykinin (acetate) inflammatory mediator
  130. C3973 Muscone anti-inflammatory effects
  131. B7830 AS 101 Immunomodulator
  132. C4592 ATB-337 hybrid molecule of an H2S donor and the NSAID diclofenac
  133. C4050 6α-methyl-11β-Hydroxyprogesterone corticosteroid and anti-inflammatory

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