Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histamine is a mediator of allergic inflammation released mainly from mast cells. Although histamine strongly increases vascular permeability, its precise mechanism under in vivo situation remains unknown. We here attempted to reveal how histamine induces vascular hyperpermeability focusing on the key regulators of vascular permeability, blood flow and endothelial barrier. Degranulation of mast cells by antigen-stimulation or histamine treatment induced vascular hyperpermeability and tissue swelling in mouse ears. These were abolished by histamine H1 receptor antagonism. Intravital imaging showed that histamine dilated vasculature, increased blood flow, while it induced hyperpermeability in venula. Whole-mount staining showed that histamine disrupted endothelial barrier formation of venula indicated by changes in vascular endothelial cadherin (VE-cadherin) localization at endothelial cell junction. Inhibition of nitric oxide synthesis (NOS) by L-NAME or vasoconstriction by phenylephrine strongly inhibited the histamine-induced blood flow increase and hyperpermeability without changing the VE-cadherin localization. In vitro, measurements of trans-endothelial electrical resistance of human dermal microvascular endothelial cells (HDMECs) showed that histamine disrupted endothelial barrier. Inhibition of protein kinase C (PKC) or Rho-associated protein kinase (ROCK), NOS attenuated the histamine-induced barrier disruption. These observations suggested that histamine increases vascular permeability mainly by nitric oxide (NO)-dependent vascular dilation and subsequent blood flow increase and maybe partially by PKC/ROCK/NO-dependent endothelial barrier disruption.
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PMID:Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo. 2615 31

This article aims to review the literature regarding the immune response to fungi in diabetic patients with invasive fungal rhinosinusitis. Systematic searches of Medline, EMBASE, and Cochrane Library databases were performed to include articles from 1988 to 2019 which assessed 'immune response to fungi in normal host', 'immune deficiency in diabetes mellitus', or 'immune response to fungi in diabetic patients'. Fungal cell wall activated pattern recognition receptors, resulting in recruitment of innate immune cells and an adaptive immune response. In diabetes mellitus, the expression of class I major histocompatibility complex was reduced. A hyperglycemic state decreased vascular dilation and the formation of neutrophil extracellular traps. The structure of complement was altered with consequent inhibition of complement fixation to bacteria. The balance between complement activation and restriction was broken. Hyperglycemia activated protein kinase C which inhibited neutrophil migration, decreased production of polymorphonuclear cells, decreased chemotaxis and decreased phagocytic activity. Germination and filamentous growth of the fungus within a diabetic host caused angioinvasion, vascular thrombosis and necrosis. Patients with diabetic ketoacidosis had elevated levels of serum iron which regulated endothelial cell damage. Iron and the overexpression of glucose-induced glucose-regulated protein 78 enhanced the susceptibility of endothelial cells to fungi and induced fungal invasion. In summary, associations among the immunopathology of diabetes, the pathophysiology of fungal infections, and the therapeutic outcomes must be considered in clinical practice. In diabetic patients, both the humoral and cellular immune responses of innate and adaptive immune systems were defective. Treatments should aim for the immune function restoration.
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PMID:Immune response to fungi in diabetic patients with invasive fungal rhinosinusitis. 3306 69