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
- 5-Lipoxygenase(11)
- TLR(15)
- Papain(1)
- PGDS(1)
- PGE synthase(3)
- SIKs(1)
- IκB/IKK(37)
- AP-1(1)
- KEAP1-Nrf2(11)
- NOD1(1)
- TLR(9)
- NF-κB(18)
- Interleukin Related(5)
- 15-lipoxygenase(2)
- Others(10)
- Cat.No. Product Name Information
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GC12578
(R)-Lisofylline
anti-inflammatory agent
-
GC11867
(S)-Lisofylline
inactive optical enantiomer of (R)-LSF, an anti-inflammatory agent
-
GC13662
(±)-Lisofylline
anti-inflammatory agent
-
GC17951
2-TEDC
5-, 12-, and 15-lipoxygenase inhibitor
-
GC15355
2-Trifluoromethyl-2'-methoxychalcone
Nrf2 activator
-
GC10290
6α-methyl-11β-Hydroxyprogesterone
corticosteroid and anti-inflammatory
-
GP10060
a-MSH, amide
Melanocyte-stimulating hormones
-
GC17416
ACHP
IκB kinase inhibitor
-
GC16120
AI-3
Nrf2/Keap1 and Keap1/Cul3 interaction inhibitor
-
GP10015
alpha-1 antitrypsin fragment
Protease inhibitor
-
GP10008
alpha-1 antitrypsin fragment 235-243 [Homo sapiens]/[Papio hamadryas]/[Cercopithecus aethiops]
Protease inhibitor
-
GP10099
amyloid A protein fragment [Homo sapiens]
Apolipoproteins related to HDL in plasma
-
GN10718
Andrographolide
NF-κB signaling Inhibitor
-
GP10124
Anti-Inflammatory Peptide 1
PLA2 inhibitor
-
GC17659
AS 101
Immunomodulator
-
GC12537
ATB-337
hybrid molecule of an H2S donor and the NSAID diclofenac
-
GC16245
ATB-343
hybrid molecule of an H2S donor and the NSAID indomethacin
-
GC15371
Bardoxolone
Once-a-day treatment for CKD
-
GC10345
Bay 11-7085
NK-κB activation inhibitor
-
GC13035
Bay 11-7821
IKK/NF-κB/TNFα inhibitor