bp(GO:"inflammatory response")
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
Modulation by nicotine of inflammatory responses in the intestines is much better reported. Early studies found that patients with ulcerative colitis who stopped smoking tobacco developed the disease or exhibited more severe disease progression, which was ameliorated by either returning to smoking (58, 401, 466), or, in some cases, administering nicotine through transdermal patches (313).In contrast, patients with Crohn’s disease experience much more severe disease when smoking (401). PubMed:19126755
There is current evidence that nAChRs present in skin cells modulate the responses triggered by inflammatory stimuli applied to the skin (354). Smoking is a welldefined risk factor in delayed wound healing and possibly the development of premature facial wrinkling (226). PubMed:19126755
In addition, viral transduction did not induce any neuroinflammation, as shown in WT noninjected mice (Fig. 3A and D) PubMed:27522251
An inhibition of TNFa induced STAT3 (Mann–Whitney U=0, Z=-2.121, P=0.034), and p65 NFkB phosphorylation (Mann–Whitney U=0, Z=-2.121, P=0.034) was observed in these cells following the anatabine treatment (Fig. 4) suggesting that anatabine may also mediate its anti-inflammatory activity independently of nicotinic acetylcholine receptor expression PubMed:23178521
Nicotine has been shown to modulate inflammation by affecting STAT3 phosphorylation (Chatterjee et al., 2009; Hosur and Loring, 2011) and by opposing NFkB activation (Leite et al., 2010; Zhou et al., 2010) PubMed:23178521
Ubiquitin-mediated proteolysis of a variety of cellular proteins plays an important role in many basic cellular processes. Among these are regulation of cell cycle and division, differentiation and development, involvement in the cellular response to stress and extracellular effectors, morphogenesis of neuronal networks, modulation of cell surface receptors, ion channels and the secretory pathway, DNA repair, transcriptional regulation, transcriptional silencing, long-term memory, circadian rhythms, regulation of the immune and inflammatory responses,and biogenesis of organelles PubMed:14556719
a report by Hoffmann et al. showed that fibrillar a-syn induced a more pronounced inflammatory response in microglial cells [61]. PubMed:28803412
Kim et al. demonstrated that a-syn oligomers lead to microglial inflammatory responses via TLR2 activation [74]. PubMed:28803412
These results raise the possibility that pyrrolopyrimidine compounds, such as antalarmin, which antagonize CRH at the level of its own receptor, have therapeutic potential in some forms of inflammation. PubMed:8940412
Corticotropin-releasing hormone (CRH) secreted from the hypothalamus is the major regulator of pituitary ACTH release and consequent glucocorticoid secretion. CRH secreted in the periphery also acts as a proinflammatory modulator. PubMed:8940412
NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037
NFkB regulates the pro-survival, pro-inflammatory SASP gene expression profile characteristic of cellular senescence (Salminen & Kaarniranta, 2011) PubMed:30126037
NFkB regulates the pro-survival, pro-inflammatory SASP gene expression profile characteristic of cellular senescence (Salminen & Kaarniranta, 2011) PubMed:30126037
Activated microglia has a double effect on AD progression (Li et al. 2014). On the one hand, they can release some proinflammatory cytokines, stimulating inflammatory response and ultimately leading to neuronal injuries and death PubMed:29626319
During Abeta-associated inflammation, reactive nitrogen and oxygen species are generated that can cause neuronal dysfunction and death (34-37). Prevalent among these species is peroxynitrite (ONOO-) PubMed:16566606
Messenger RNA analysis of two pro-inflammatory markers such as IL-1β and inducible nitric oxide synthase (iNOS) indicate that TAUP301L expression induce Il-1β (Fig. 6D) and iNOS (Fig. 7D) mRNA expression in both genotypes and DMF treatment decreased this expression only in Nrf2+/+ mice. PubMed:29121589
Messenger RNA analysis of two pro-inflammatory markers such as IL-1β and inducible nitric oxide synthase (iNOS) indicate that TAUP301L expression induce Il-1β (Fig. 6D) and iNOS (Fig. 7D) mRNA expression in both genotypes and DMF treatment decreased this expression only in Nrf2+/+ mice. PubMed:29121589
Messenger RNA analysis of two pro-inflammatory markers such as IL-1β and inducible nitric oxide synthase (iNOS) indicate that TAUP301L expression induce Il-1β (Fig. 6D) and iNOS (Fig. 7D) mRNA expression in both genotypes and DMF treatment decreased this expression only in Nrf2+/+ mice. PubMed:29121589
In addition, IL-1α, which also activates IL-1R, could contribute to the inflammatory response in vivo. PubMed:23702978
Interleukins, in particular IL-1β and IL-18, are upregulated in AD brain, and the overexpression of IL-1β or IL-18 is critical for the onset of the inflammatory process (Rubio-Perez and Morillas-Ruiz, 2012), and both mediate the expression of a vast array of inflammatory genes (Weber et al., 2010) PubMed:24561250
Interleukins, in particular IL-1β and IL-18, are upregulated in AD brain, and the overexpression of IL-1β or IL-18 is critical for the onset of the inflammatory process (Rubio-Perez and Morillas-Ruiz, 2012), and both mediate the expression of a vast array of inflammatory genes (Weber et al., 2010) PubMed:24561250
Pattern recognition receptors such as the TLR4 receptor are expressed in the brain’s own immune cells like microglia and astrocytes that induce inflammation via cytokine secretion [38]. PubMed:27314526
P2X7 activation is followed by a number of downstream events, including release of pro-inflammatory mediators, cell death, and proliferation. PubMed:27314526
Furthermore, anatabine has been recently shown to inhibit nuclear factor-kB(NF-kB) activation and reduce neuroinflammation in a mouse model of Alzheimer disease (15). PubMed:22807490
We have shown previously that anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. PubMed:26010758
We have shown previously that anatabine displays some anti-inflammatory properties by reducing the activation of NFκB and STAT3 [17,18]. PubMed:26010758
We have previously shown that anatabine inhibits STAT3 and NFκB activation [18] resulting in decreased neuroinflammation in a mouse model of multiple sclerosis. PubMed:26010758
Additionally, PN regulation is integrated with pathways involved in inflam- mation, response to oxidative stress, caloric restriction/starvation, and longevity. PubMed:23746257
Glial activation, pro-inflammatory gene expression and elevated secretion of IL-1, IL-6 and TNF- are consequences of high A levels [30,31]. PubMed:29179999
Curcumin showed several anti-inflammatory characteristics. It deploys various cytokine-inhibitory, anti-inflammatory activities and decreases the expression levels of COX-2, LOX, and iNOS. Moreover, the expression of the pro-inflammatory cytokines, for instance, TNF-, IL-1, -2,-6, -8, and -12 and the neurotoxic factors were suppressed by curcumin in lipopolysaccharide (LPS)-stimulated monocytes and alveolar macrophages [103]. PubMed:29179999
Inflammation caused by LPS was reduced with treatment of punicalaginin RAW264.7 macrophages, astrocytes and microglial BV-2 cells PubMed:29179999
Furthermore, A induced NF-B activity in glial and neuronal cells. NF-B is involved in inflammatory responses and is expressed in brains of AD patients [32]. PubMed:29179999
ROS activate various downstream signaling molecules, such as PKC and mitogen-activated protein kinases (MAPKs) that induce nuclear translocation of NF-B and the expression of pro-inflammatory genes [41]. PubMed:29179999
Inflammation is a key pathological hall mark of AD [61,62], NF-κB is considered as a primary regulator of inflammatory processes [10]. PubMed:27288790
Various endogenous and exogenous stimuli activate NF-κB enhancing transactivation of inflammatory molecules and production of free radicals in glial cells PubMed:25652642
Differently from biliverdin and CO, which have anti-inflammatory effects (Otterbein et al., 2000; Baranano et al., 2002), free Fe is highly oxidative and can promote free radicals generation through the Fenton reaction, which catalyzes hydroxyl radicals from the reaction of Fe with H2O2 (Fenton, 1894). PubMed:24904418
Importantly, protoporphyrin did not induce TNFα, suggesting a critical proinflammatory role for iron within the heme moiety (supplemental Figure 8). PubMed:26675351
Another pathogenic mechanism involves the release of iron from cell-free hemoglobin with consecutive radical formation, which in turn can modify lipids, proteins, and DNA, leading to inflammation [39]. PubMed:29956069
As a component of hemoglobin, free heme is released when hemolysis or extensive cell damage occur which results in inflammatory response. PubMed:24464629
Hemin induces expression of the adhesion molecules on endothelial cells [7, 8] and enables firm neutrophil attachment to the endothelium and initiation of an inflammatory response [9, 10]. PubMed:28716864
These experiments confirm a number of earlier reports and support the idea that certain solutions derived from purified/crystalline heme have the potential to induce weak TLR4-mediated inflammatory responses in macrophages in the complete absence of plasma derived proteins. PubMed:29610666
As a part of the inflammatory response after injury, oxidative stress due to formation of reactive oxygen species (ROS) is involved both in direct damage of cartilage components and as integral factors in cell signaling leading to cartilage degradation (Henrotin et al., 2003). PubMed:30505280
Differently from biliverdin and CO, which have anti-inflammatory effects (Otterbein et al., 2000; Baranano et al., 2002), free Fe is highly oxidative and can promote free radicals generation through the Fenton reaction, which catalyzes hydroxyl radicals from the reaction of Fe with H2O2 (Fenton, 1894). PubMed:24904418
Our data support the idea that heme-induced phenotypic switching of macrophages toward a proinflammatory phenotype can contribute to the exacerbation of inflammation and chronic tissue injury in hemolytic disorders and that Hx therapy could alleviate these pathophysiologic consequences by preventing macrophage inflammatory activation. PubMed:26675351
However, similar to Hb, heme-albumin did not induce an inflammatory response in macrophages or endothelial cells in the presence of low concentrations of serum. PubMed:29610666
Taken together, these data demonstrate that Hx limits macrophage heme overload and prevents the prooxidant and proinflammatory effects triggered by heme in cellular assays and in vivo. PubMed:26675351
Taken together, these data suggest that Hx administration decreases heme-driven proinflammatory activation of macrophages. PubMed:26675351
In conclusion, an Hx-based therapy shows beneficial effects, in that it counteracts heme-induced proinflammatory activation of macrophages and attenuates some of its pathophysiologic consequences, such as chronic inflammation, hepatic fibrosis, and apoptosis (Figure 7E). PubMed:26675351
Our data support the idea that heme-induced phenotypic switching of macrophages toward a proinflammatory phenotype can contribute to the exacerbation of inflammation and chronic tissue injury in hemolytic disorders and that Hx therapy could alleviate these pathophysiologic consequences by preventing macrophage inflammatory activation. PubMed:26675351
Other studies demonstrated that heme can trigger the activation of Toll-like receptor 4 and inflammasomes, thus leading to inflammatory reactions.5,35–37 PubMed:26794659
The released heme can activate the innate immune pattern recognition receptor toll-like receptor 4 (TLR4) on inflammatory cells, platelets and endothelium, promoting a pro-inflammatory and pro-coagulant phenotype, ultimately leading to vaso-occlusion, ischemia-reperfusion physiology, tissue injury, and pain in murine models of SCD [5, 7±10]. PubMed:29694434
IL-1b participates in a robust inflammatory response. PubMed:24464629
Lately, much evidence has emerged to support a central role for participation of local inflammatory pathways in the disease processes (Scanzello, 2017), particularly so after knee injury (Goldring and Otero, 2011). PubMed:30505280
Our data support the idea that heme-induced phenotypic switching of macrophages toward a proinflammatory phenotype can contribute to the exacerbation of inflammation and chronic tissue injury in hemolytic disorders and that Hx therapy could alleviate these pathophysiologic consequences by preventing macrophage inflammatory activation. PubMed:26675351
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
We did not detect any glia or microglia activation in WT-APP (Fig. 3C and F) compared with WT-GFP (Fig. 3B and E), meaning that the neuroinflammation does not play a role in the memory deficit we observed PubMed:27522251
Corticotropin-releasing hormone (CRH) secreted from the hypothalamus is the major regulator of pituitary ACTH release and consequent glucocorticoid secretion. CRH secreted in the periphery also acts as a proinflammatory modulator. PubMed:8940412
These results raise the possibility that pyrrolopyrimidine compounds, such as antalarmin, which antagonize CRH at the level of its own receptor, have therapeutic potential in some forms of inflammation. PubMed:8940412
NFkB regulates the pro-survival, pro-inflammatory SASP gene expression profile characteristic of cellular senescence (Salminen & Kaarniranta, 2011) PubMed:30126037
For example, ongoing inflammation can trigger various cell stress-response pathways, including overexpression of the secreted glycoprotein Dickopff-1 (DKK-1). DKK-1 up-regulates GSK-3β activity, promotes tau hyper-phosphorylation, NFT formation and neuronal degeneration. Thus, DKK-1 inhibits Wnt signalling in a manner similar to Aβ, and thereby fosters a self-sustaining feedback loop resulting in cellular injury PubMed:18494933
During Abeta-associated inflammation, reactive nitrogen and oxygen species are generated that can cause neuronal dysfunction and death (34-37). Prevalent among these species is peroxynitrite (ONOO-) PubMed:16566606
Additionally, PN regulation is integrated with pathways involved in inflam- mation, response to oxidative stress, caloric restriction/starvation, and longevity. PubMed:23746257
Excessive amounts of ROS may also arise from inflammatory processes [75]. PubMed:24563850
Furthermore, A induced NF-B activity in glial and neuronal cells. NF-B is involved in inflammatory responses and is expressed in brains of AD patients [32]. PubMed:29179999
As a component of hemoglobin, free heme is released when hemolysis or extensive cell damage occur which results in inflammatory response. PubMed:24464629
Hemin induces expression of the adhesion molecules on endothelial cells [7, 8] and enables firm neutrophil attachment to the endothelium and initiation of an inflammatory response [9, 10]. PubMed:28716864
IL-1b participates in a robust inflammatory response. PubMed:24464629
Importantly, protoporphyrin did not induce TNFα, suggesting a critical proinflammatory role for iron within the heme moiety (supplemental Figure 8). PubMed:26675351
Taken together, these data suggest that Hx administration decreases heme-driven proinflammatory activation of macrophages. PubMed:26675351
In conclusion, an Hx-based therapy shows beneficial effects, in that it counteracts heme-induced proinflammatory activation of macrophages and attenuates some of its pathophysiologic consequences, such as chronic inflammation, hepatic fibrosis, and apoptosis (Figure 7E). PubMed:26675351
Our data support the idea that heme-induced phenotypic switching of macrophages toward a proinflammatory phenotype can contribute to the exacerbation of inflammation and chronic tissue injury in hemolytic disorders and that Hx therapy could alleviate these pathophysiologic consequences by preventing macrophage inflammatory activation. PubMed:26675351
Our data support the idea that heme-induced phenotypic switching of macrophages toward a proinflammatory phenotype can contribute to the exacerbation of inflammation and chronic tissue injury in hemolytic disorders and that Hx therapy could alleviate these pathophysiologic consequences by preventing macrophage inflammatory activation. PubMed:26675351
Our data support the idea that heme-induced phenotypic switching of macrophages toward a proinflammatory phenotype can contribute to the exacerbation of inflammation and chronic tissue injury in hemolytic disorders and that Hx therapy could alleviate these pathophysiologic consequences by preventing macrophage inflammatory activation. PubMed:26675351
Other studies demonstrated that heme can trigger the activation of Toll-like receptor 4 and inflammasomes, thus leading to inflammatory reactions.5,35–37 PubMed:26794659
The released heme can activate the innate immune pattern recognition receptor toll-like receptor 4 (TLR4) on inflammatory cells, platelets and endothelium, promoting a pro-inflammatory and pro-coagulant phenotype, ultimately leading to vaso-occlusion, ischemia-reperfusion physiology, tissue injury, and pain in murine models of SCD [5, 7±10]. PubMed:29694434
However, similar to Hb, heme-albumin did not induce an inflammatory response in macrophages or endothelial cells in the presence of low concentrations of serum. PubMed:29610666
Lately, much evidence has emerged to support a central role for participation of local inflammatory pathways in the disease processes (Scanzello, 2017), particularly so after knee injury (Goldring and Otero, 2011). PubMed:30505280
As a part of the inflammatory response after injury, oxidative stress due to formation of reactive oxygen species (ROS) is involved both in direct damage of cartilage components and as integral factors in cell signaling leading to cartilage degradation (Henrotin et al., 2003). PubMed:30505280
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.