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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. GC45194 α-(difluoromethyl)-DL-Arginine

    Bacteria synthesize the cellular growth factor putrescine through a number of pathways.

  3. GC41183 α-Carotene α-Carotene is a precursor of vitamin A that has been found in various fruits and vegetables.
  4. GC48279 α-D-Glucose-1-phosphate (sodium salt hydrate)
  5. GC45204 α-Ecdysone

    α-Ecdysone is a prohormone of 20-hydroxy ecdysone, an insect-molting, ecdysteroid hormone.

  6. GC45206 α-GalCer analog 8

    α-Galactosylceramide analog 8 (α-GalCer analog 8) is a triazole derivative of α-galactosylceramide.

  7. GC40262 α-Humulene α-Humulene is a sesquiterpene that has been found in C.
  8. GC45601 α-Linolenic Acid ethyl ester-d5  
  9. GC48292 α-MSH (human, mouse, rat, porcine, bovine, ovine) (trifluoroacetate salt)
  10. GC41499 α-Phellandrene α-Phellandrene is a cyclic monoterpene that has been found in various plants, including Cannabis, and has diverse biological activities.
  11. GC37999 β-Anhydroicaritin β-Anhydroicaritin 提取自 Boswellia carterii Birdware,具有重要的生物学和药理学作用,例如抗骨质疏松症,雌激素调节和抗肿瘤特性。β-Anhydroicaritin 改善牙周组织的降解,抑制糖尿病大鼠 TNF-α 和 MMP-3 的合成和分泌。β-Anhydroicaritin 减少腹膜炎小鼠 NO,IL-10,TNF-α,MCP-1 和 IL-6 的过量产生。β-Anhydroicaritin 抑制细胞内 Ca2+ 的升高,并显着降低 iNOS 蛋白的表达。
  12. GC45225 β-Apooxytetracycline β-Apooxytetracycline is a potential impurity found in commercial preparations of oxytetracycline.
  13. GC48920 β-Carboline-1-carboxylic Acid
  14. GC48298 β-Defensin-2 (human) (trifluoroacetate salt)
  15. GC45230 β-Defensin-3 (human) (trifluoroacetate salt) β-Defensin-3 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts.
  16. GC45231 β-Defensin-4 (human) (trifluoroacetate salt) β-Defensin-4 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts.
  17. GC41623 β-Elemonic Acid β-Elemonic acid is a triterpene isolated from Boswellia (Burseraceae) that exhibits anticancer activity.
  18. GC41502 β-Myrcene β-Myrcene is a terpene that has been found in Cannabis and has antioxidative properties.
  19. GC45604 β-Rubromycin  
  20. GC48312 γ-Glu-Cys (ammonium salt)
  21. GC40790 γ-Linolenic Acid ethyl ester γ-Linolenic acid (GLA) is an ω-6 fatty acid which can be elongated to arachidonic acid for endogenous eicosanoid synthesis.

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