A review of inflammatory mediators Flashcards
Groups of Eiconosanoids?
prostaglandins, thromboxanes, leukotrienes, epoxides
What do Eiconsanoids do?
control cellular function in response to multiple signals (inflammation)
act through paracrine and autocrine function thus affecting cells that produce them or adjacent cells
Synthesis of inflammtory mediators?
- stimulus/ligand binds to tansmembrane receptor
- cause an increase in PL-A2 and PL-C which cleaves SN2 and releases arachidonic acid
- PL-c through IP3 causes signal transduction to increase the stimulus and DAG to cleave…
Higher concentration of which prostalgandin in arthritis?
PG-A2
Most common phospholpases?
A2, C
IP3 causes release of?
Calcium
what does PLC or phospholipase C do?
converstion of PIP2 to IP3 and DAG
DAG cause increase of?
PKC
From arachidonic acid what enzyme makes prostaglandins?
cyclooxgenase
What does lipoxygenase convert arachidonic acid to? what inhibits it?
leukotrienes
Leukotriene inhibitors
What inhibits cyclooxygenase?
glucocortiocoids
COX-inhibitors
Antiinflammtory Prostaglandin?
PGE3
TXA2?
made from arachidonic acid/PGH2 enzyme TXA2 produced in platelets vasoconstrict hemostasis
PGI?
from arachidonic acid/PGH2 enzyme PGI synthase produced in endotherlial cells vasodilation inhibit hemostasis
PGE synthase?
PGH2 to PGE
PGD synthase?
PGH2 to PGD
NSaids?
nonspecific inhibit all PG synthesis
tissue specific
Prostaglandin found in mast cells, brain, airways?
PGD2
Prostaglandin found in brain, kidneys, VSMCs, platelets?
PGE2
Cyclooxygenase?
3 cox enzymes
cox 3 is a splice variant of COX1
diff tissues express vary levels of COX1/2
COX1 is considered a constituitive enzyme found in most tissues and COX 2 is an inducible enzyme
Consitutive enzyme? inducible enzyme?
COX1 COX2
Acetaminophen works on?
cox3 in the brain
COX3 part of eiosanoid signaling?
no
Aspirin biochemical mechanism?
Acetylsalicylate binds to Active cyclo-oxygenase to form inactive Cyclo-oxygenase
releases Salicylate at the same time
Does acetaminophen or ibuprofen inactive cyclooxygenase?
no
Uric acid crystals do what to osteoblasts?
increase
increased levels of PGE2 does what to osteoclast precursors?
increase
Describe action of prostaglandins?
shorted lived, quick response, g protein coupled receptors
Steroidogenic acture regulatory protein?
sTAR endocytosis brings LDL into the cell
Adrenal gland?
located on the kidneys
responsible for steroid hormone synthesis
3 layers
medulla of the glad is important for catecholamines
Rate limit step in cholesterol synthesis?
CYP11A1, Cholesterol to pregnenolone
Pregnenolone to Progesterone?
3beta HSD
Progesterone to 17alpha hydroxy progesterone?
CYP17
CYP17 also?
Pregnenolone to 17alpha hydroxy pregnenolone
17alpha hydroxy progesterone to cortisol?
CYP21A, CYP11B1
ACTH induces?
adrenal cortex to make steroids
Zona glomerulosa?
ACTH can stim aldosterone synthesis but this area is primarily regulated by Ang II and extracellular K
has receptors for AngII and expresses CYP11B2
HPA axis?
Hypothalamus releases CRH from CRH neurons
Anterior Pituitary releases ACTH from Corticotropes
Andrenal cortex releases cortisol from Fasiculata cells
Regulates Hypothalamus?
increase release ACh, 5-HT, NE, IL-1, IL-2, IL-6, TNFalpha
decrease release NE, GABA, cortisol
Regulate Anterior pituitary?
increase release IL-1, IL-2, IL-6, TNFalpha
decrease release cortisol
Cortisol release controls?
negative feedback to Anterior pituitary and Hypothalamus, and to Immune system, lymphocytes, macrophages, monocytes, neutrophils
Immune system, etc release?
IL-1, IL-2, IL-6, TNFalpha
all stim Hypothalamus and Anterior pituitary
Gluccocoritcoid effect on immune cells? (cortisol)
decrease cytokine production form macrophages
inhibit histamine release and prostaglandins from mast cells, suppress t cell activation, and inhibit release of histamine, prostaglandins, and leukotrienes from eosinophils
Glucocorticoids affect metabolism?
increase vitamin D, decrease glucose uptake, increase glycogen synthase, increase parathyroid hormone, increase IGF-1
Androstenedione to Testosterone?
17beta HSD
Testorsterone to estradiol?
aromatase