a(MESH:Cytokines)
This particular dosage was selected from a previous study showing that this dosage is efficient at lowering brain cytokine levels in a mouse model of Alzheimer’s disease displaying chronic neuroinflammation PubMed:23383175
Reduction of A expression and cytotoxic-ity stimulated by A in neuroblastoma cells and the inhibition of inflammatory cytokines, ROS and NO in microglial cells were detected upon treatment with -tocopherol [210]. PubMed:29179999
Furthermore, it inhibited pro-inflammatory cytokines, which were induced by A 25-35/IFN- in microglia cells [248]. PubMed:29179999
Tetrandrine inhibited the activity of NF-B and down-regulated the expression of pro-inflammatory cytokines [178–180]. PubMed:29179999
Inhibition of NF-κB leads to decreased induction of cytokines and chemokines by IL-1β and TNF-α. PubMed:27288790
Inhibition of NF-κB leads to decreased induction of cytokines and chemokines by IL-1β and TNF-α. PubMed:27288790
Inhibition of NF-κB leads to decreased induction of cytokines and chemokines by IL-1β and TNF-α. PubMed:27288790
Excessive accumulation of Aβ1-42 stimulates microglial cells by signaling via receptor associated advanced glycation end products (RAGE) and peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphorylates IKK proteins, and enhances NF-κB mediated transactivation of inflammatory cytokines and neurotoxic molecules such as glutamate and reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) [12] (Fig 2B) PubMed:25652642
Furthermore, cytokine secretion depends on the coordinated iron in the porphyrin ring (Figueiredo et al, 2007), and nuclear factor-jB (NF-jB), MAPKs activation and ROS are essential for the increase in cytokine production induced by haem (Fernandez et al, 2010). PubMed:25307023
Free heme has been proved possess pro-inflammatory activities, such as leukocyte activation, migration and infiltration, adhesion molecules activation, and cytokines and acute phase proteins induction [17, 18]. PubMed:24464629
Heme amplifies cytokines induced by cell surface receptors (TLR2, TLR4, TLR5), endosome receptors (TLR3, TLR9), and cytosolic receptors (NOD1 and NOD2). PubMed:24904418
Transfusion of RBCs after prolonged refrigerator storage is associated with haemolysis (Donadee et al, 2011; Hod et al, 2011) and enhances cytokine secretion in response to lipopolysaccharide (LPS) administration (Hod et al, 2010). PubMed:25307023
Furthermore, cytokine secretion depends on the coordinated iron in the porphyrin ring (Figueiredo et al, 2007), and nuclear factor-jB (NF-jB), MAPKs activation and ROS are essential for the increase in cytokine production induced by haem (Fernandez et al, 2010). PubMed:25307023
Moreover, ferrylHb is unable to induce cytokine secretion by endothelial cells (Silva et al., 2009), another difference to heme which induces IL-8 production (Natarajan et al., 2007). PubMed:24904418
Similarly to heme, Hz also induces the production of several inflammatory mediators by macrophages such as cytokines and chemokines, and induces leukocytes migration (reviewed by Olivier et al., 2014). PubMed:24904418
Finally, the cytokines produced through these pathways can then affect endothelial activation, leucocyte recruitment, and ultimately thrombotic risk. PubMed:25307023
Furthermore, haem-induced release of P-selectin and VWF is mediated by TLR4 and NFkB signalling. PubMed:25307023
Hb synergizes with LPS enhancing the production of pro-inflammatory cytokines by macrophages (Yang et al., 2002). PubMed:24904418
Furthermore, cytokine secretion depends on the coordinated iron in the porphyrin ring (Figueiredo et al, 2007), and nuclear factor-jB (NF-jB), MAPKs activation and ROS are essential for the increase in cytokine production induced by haem (Fernandez et al, 2010). PubMed:25307023
However, with A1M increased in both synovial fluid and serum in AIA, the present study further suggests that, in addition to heme and ROS, A1M may be regulated by inflammatory cytokines. PubMed:30505280
Furthermore, cytokine secretion depends on the coordinated iron in the porphyrin ring (Figueiredo et al, 2007), and nuclear factor-jB (NF-jB), MAPKs activation and ROS are essential for the increase in cytokine production induced by haem (Fernandez et al, 2010). PubMed:25307023
Haem increases lethality and cytokine secretion induced by LPS in vivo and enhances cytokine secretion by macrophages stimulated with various innate immune receptor agonists (e.g., TLR2, TLR9, TLR3, and nucleotide-binding oligomerization domain (NOD) agonists) (Fernandez et al, 2010). PubMed:25307023
Haem increases lethality and cytokine secretion induced by LPS in vivo and enhances cytokine secretion by macrophages stimulated with various innate immune receptor agonists (e.g., TLR2, TLR9, TLR3, and nucleotide-binding oligomerization domain (NOD) agonists) (Fernandez et al, 2010). PubMed:25307023
Haem increases lethality and cytokine secretion induced by LPS in vivo and enhances cytokine secretion by macrophages stimulated with various innate immune receptor agonists (e.g., TLR2, TLR9, TLR3, and nucleotide-binding oligomerization domain (NOD) agonists) (Fernandez et al, 2010). PubMed:25307023
Haem increases lethality and cytokine secretion induced by LPS in vivo and enhances cytokine secretion by macrophages stimulated with various innate immune receptor agonists (e.g., TLR2, TLR9, TLR3, and nucleotide-binding oligomerization domain (NOD) agonists) (Fernandez et al, 2010). PubMed:25307023
Under different envi- ronmental conditions such as Aβ/ROS/cytokines accumulation, the IκB kinase (IKK) complex becomes activated and mediates the phosphoryla- tion of IκBs, then IκBs are degradated and the remaining NF-κB dimer is activated and thus translocates to the nucleus where it binds to the DNA consensus sequence of various target genes [9–11]. PubMed:27288790
Moreover, miRNA-155 is strongly and rapidly up-regulated by inflammatory cytokines and also is an inducible miRNA under transcriptional control by NF-κB. PubMed:27288790
The cytokines released can further lead to pronounced peripheral vasodilation with arterial hypotension by activating the inducible nitric oxide (NO) synthase (iNOS) and the subsequent formation of NO [30]. PubMed:29956069
Free heme has been proved possess pro-inflammatory activities, such as leukocyte activation, migration and infiltration, adhesion molecules activation, and cytokines and acute phase proteins induction [17, 18]. PubMed:24464629
Furthermore, cytokine secretion depends on the coordinated iron in the porphyrin ring (Figueiredo et al, 2007), and nuclear factor-jB (NF-jB), MAPKs activation and ROS are essential for the increase in cytokine production induced by haem (Fernandez et al, 2010). PubMed:25307023
Furthermore, cytokine secretion depends on the coordinated iron in the porphyrin ring (Figueiredo et al, 2007), and nuclear factor-jB (NF-jB), MAPKs activation and ROS are essential for the increase in cytokine production induced by haem (Fernandez et al, 2010). PubMed:25307023
Finally, the cytokines produced through these pathways can then affect endothelial activation, leucocyte recruitment, and ultimately thrombotic risk. PubMed:25307023
Finally, the cytokines produced through these pathways can then affect endothelial activation, leucocyte recruitment, and ultimately thrombotic risk. PubMed:25307023
Platelets may be activated during haemolysis by several different mechanisms involving decreased NO levels, increased pro-inflammatory cytokines and mediators, and ROS. PubMed:25307023
The cytokines released can further lead to pronounced peripheral vasodilation with arterial hypotension by activating the inducible nitric oxide (NO) synthase (iNOS) and the subsequent formation of NO [30]. PubMed:29956069
Furthermore, a massive release of cytokines will shift the balance between pro- and anti-coagulatory factors in the blood, which will lead to increased coagulation of the blood (coagulopathy). PubMed:29956069
However, with A1M increased in both synovial fluid and serum in AIA, the present study further suggests that, in addition to heme and ROS, A1M may be regulated by inflammatory cytokines. PubMed:30505280
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