Images under the category inflammation
Figure 1Immunological mechanisms of central nervous system and periphery communication Schematic view of the four pathways by which the CNS communicates with the periphery: passage of immune mediators and pathogens through CVO, activation of the perivascular macrophages that enhances cytokines release within the CNS, activation of IL-1 receptors in vascular endothelial cells and perivascular macrophages of cerebral venules, and stimulation of the afferent neurons by pathogens at the periphery producing the passage of cytokines through the BBB by the ST mechanism.
Figure 2Potential mechanisms of kidney-brain cross-talk Schematic view of the potential mechanisms related to the cross-talk between the kidney and brain. CKD or acute kidney injury (AKI) increases serum levels of chemokines and cytokines. Systemic and locally produced Ang II stimulates cytokine release by the kidneys. Inflammatory molecules are then transported to CNS via the neural route and humoral route. These molecules cross the BBB, which was disrupted by inflammation. In CNS, cytokines and chemokines activate immune cells, neurons, and glial cells leading to more release of inflammatory molecules, which locally interact with neurotrophic factors and with reactive species of oxygen, thus contributing to neuropsychiatric disorders.
Figure 1The phagocyte NADPH oxidase (NOX2) is a crucial enzyme in antimicrobial host defence and in regulating inflammation Activation of NOX2 requires translocation of the cytoplasmic subunits p40phox, p47phox and p67phox and Rac to the membrane-bound cytochrome comprised of p22phox and gp91phox. Molecular oxygen is converted to superoxide anion, which can be converted to downstream metabolites with antimicrobial activity, including H2O2 and hydroxyl anion. In neutrophils, MPO converts H2O2 to hypohalous acid.
Figure 1Schematic overview of cellular iron transport in cardiomyocytes The role of DMT-1 as well as other transporters such as LTCC and TTCC as possible portals for iron into cardiomyocytes. In addition Tf binds to TfRs on the external surface of the cell. The role of NGAL is to donate iron to cells via the NGAL-R. Internalization of NGAL and its receptor leads to the uptake of iron from the siderophore–iron complex, although the exact mechanism remains unclear. However, accumulation of iron subsequently induces mitochondrial dysfunction, oxidative stress, ER stress and autophagy in cardiomyocytes. Additional details about the specific information are given in the text.
Figure 1PECAM-1-mediated signal transduction The PECAM-1 extracellular domain is involved in the interactions between various membrane molecules including PECAM-1 itself. Homophilic interaction between two PECAM-1 isoforms without exon 14 regulates cell–cell adhesion and AJ formation, although exon 14-containing isoforms mediate heterophilic interaction with other molecules on the cell surface, having an impact on various cellular processes, including aggregation and transendothelial migration. These activities occur through engagement of various signalling molecules. In addition, the PECAM-1 cytoplasmic domain participates in modulation of cell adhesion and migration through interaction with various intracellular proteins (e.g. β/γ-catenin and eNOS). For additional details please see the literature [44,187].
Figure 1Type I IFN pathway in pDCs Type I IFNs can activate the transcription of IRGs through the JAK/STAT pathway. The type I IFNs can regulate almost 200 genes, whose simultaneous increased expression is referred to as the so-called IFN signature. These genes are responsible for the antiviral effects of type I IFNs and are also involved in the triggering of type I IFNs, as well as in a variety of immunomodulatory effects of type I IFNs. On the other hand, interferogenic immune complexes in autoimmune disorders can stimulate type I IFN gene transcription by engaging FcγRIIa receptors, thereby leading to higher type I IFN expression. Molecules reported to be associated with genetic susceptibility to RA are highlighted in red.
Figure 3IFNα and vascular damage IFNα is associated with vascular damage through different ways, including by promoting increased endothelial injury (direct endothelial damage, platelet activation, foam cell differentiation and plaque destabilization) and impaired endothelial repair (EPC dysfunction and Tang cell decrease). ROS, reactive oxygen species.
Figure 2The role of eHSP70 in islet physiology: an integrative hypothesis Adipose tissue expansion attracts monocyte infiltration. The new environment induces the release of pro-inflammatory cytokines (low-grade inflammation) that reduces the skeletal muscle insulin sensitivity, inducing hyperglycaemia. Additionally, chronic leptin release induces the activation of the SNS. Catecholamines produced by the SNS can stimulate the release of eHSP70 by lymphocytes, leading to chronic elevations of this protein in the plasma. The effects of eHSP70 are cell-dependent, but occur via activation of TLR2 and TLR4. Specifically in β-cells, eHSP70 induces the activation of intracellular inflammatory pathways, increasing ROS production via NOX activation and mitochondrial damage, and blunts the intracellular HSP70 synthesis machinery. ER stress and UPR occurs due to the poor iHSP70 response, finally leading to cell dysfunction and death. Infiltrated macrophages are also activated by eHSP70 and cytokines. They release IL-6 and other inflammatory factors into the microenvironment. eHSP70 acts on pancreatic α-cells, however the response is different since they respond to IL-6 differently, as described in the text, including the enhancement of iHSP70 expression. The higher chaperone capacity, along with the low presence/activity of NOX allows this cell to maintain high levels of hormone release without ER stress and UPR. FFA, free (non-esterified) fatty acid.
Figure 1A simplified schematic diagram representing TLR2 and TLR4 signalling in the diabetic kidney The release of endogenous ligands in the diabetic milieu (hyperglycaemia, dyslipidaemia and hypoxia) activates TLR2 and TLR4 in immune and kidney cells. Activation of TLR2 initiates the MyD88-dependent pathway, whereas TLR4 engagement initiates MyD88-dependent and MyD88-independent signalling pathways. However, the pathways converge in the activation of NF-κB, which is responsible for the synthesis and secretion of pro-inflammatory cytokines, chemokines, cell adhesion molecules and pro-fibrotic markers involved in inflammation and fibrosis, eventually leading to diabetic nephropathy.
Figure 5Representative example of immunohistochemistry of the left atrium from a subject with mitral regurgitation From left to right, the left atrium demonstrates infiltration of mast cells with chymase (red) in various stages of degranulation. (A) Intact mast cell; (B) mast cell release of chymase into interstitium, (C) mast cell chymase located within atrial myocyte as well as in the interstitium in magnified inset with degranulating mast cell in lower right corner. Blue, DAPI; green, desmin.
