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WEEK 9 SEM 4 > Lipid mediators of Inflammation > Flashcards

Lipid mediators of Inflammation Flashcards

1
Q

What is eicosanoids?

A

collective name for prostaglandins, thromboxane and leukotrienes

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2
Q

What 2 things can eicosanoids be split into?

A

cylooxegenases and lipooxygenases

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3
Q

What are cylooxegenases?

A

prostaglandins, thromboxanes

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4
Q

What are lipooxygenases?

A

leukotrienes-lipoxins

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5
Q

What are eicosanoids targets for?

A

NSAIDs−glucocorticoids−lipoxygenase inhibitors−leukotriene antagonists

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6
Q

What is a prostanoid?

A

prostaglandin and thromboxane

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7
Q

What are prostanoids generated from?

A

arachidonic acid

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8
Q

How is arachidonic acid produced?

A

2 pathways:
1 step pathway
direct conversion of phospholipids into arachidonic acid

2 step pathway
-phospholipids are converted to diacyl glycerol (by phospholipase C) or to phosphatidic acid (by phospholipase D)
-diacyl glycerol is converted to arachidonic acid by DAG lipase, and phosphatidic acid is converted to arachidonic acid by phospholipase A2
−these two pathways are triggered by many agents eg thrombin acting on platelets, and antigen-antibody reactions, by action of bradykinin and adrenaline

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9
Q

What enzyme is needed to convert arachidonic acid to prostanoids?

A

Cyclooxegenase (COX)

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10
Q

What is COX?

A

fatty acid attached to ER

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11
Q

What are the 2 isoforms of COX?

A

COX1 and COX2

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12
Q

What is COX 1 and what does it do?

A

always active

regulation of peripheral vascular resistance (thromboxane A2), renal blood flow (prostaglandinE2), platelet aggregation (thromboxane A2), gastric protection (prostaglandin E2)

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13
Q

What is COX 3?

A

variant of COX 1

involved in pain perception in CNS

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14
Q

What is COX 2?

A

not always active
needs to be stimulated (byIL-1b and TNF alpha)

responsible for the role of prostaglandin/thromboxane in the inflammatory response such as pain and fever

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15
Q

What is the role of COX?q

A

convert arachidonic acid to two prostaglandin endoperoxides

PGG2 and PGH2, PGG2 is not stable and is converted to PGH2

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16
Q

How is PGH2 converted to prostanoids?

A

isomerase enzyme

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17
Q

What does thromboxane synthase do?

A

converts PGH2 to thromboxane A2

−this is important in platelet aggregation

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18
Q

What is TXA2 important for?

A

platelet aggregation

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19
Q

What does prostacyclin synthase do?

A

converts PGH2 to prostacyclin PGI2

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20
Q

What is PGI2 important in?

A

vasodilation

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21
Q

What does PGE2 do?

A

vasodilator

promotes labour through cervix dilation

22
Q

What does PGD2 do?

A

bronchoconstriction

inhibits platelet aggregation

23
Q

What does PGF2a do?

A

bronchoconstriction and uterine contraction

24
Q

What do Bradykinin and adrenaline do?

A

initiators of the cascade by initiating phospholipase action at the cell membrane.

25
Q

What can inhibit the cycloxegenase pathway?

A

aspirin

26
Q

What happens if you inhibit the cycloxegenase pathway?

A

initiate the lipoxygenase pathway bc arachidonic acid needed to make leukotrines and lipoxins

27
Q

How do you get Leuketriene A4 from arachidonic acid?

A

5-lipoxygenase with the help of FLAP converts arachidonic acid to 5-HPETE which results in the first leukotriene: leukotriene A4

28
Q

What does leukotriene A4 become?

A

amino acids can be added to leukotriene to produce leukotrienes C4, D4, and E4

leukotriene A4 can also be converted to lipoxins by other lipoxygenases

29
Q

What does PPAR gamma do?

A

reduces levels of some inflammatory mediators

30
Q

What do lipoxins recruit?

A

monocytes to clear the inflammation

31
Q

What do CyPGs do?

A
  • work with lipoxins and prostaglandin D2
  • promote Phagocytosis of apoptotic cells by macrophages
  • Ihibit macrophage activation thus reducing uncontrolled tissue damage
  • reduce NF kappa B activation (by controlling the levels of I kappa B alpha which is an inhibitor of NK kappa B) which helps to reduce activation of inflammatory genes
32
Q

What do mast cells make?

A

PGD4

33
Q

wHAT DO ENDOTHELIAL CELLS MAKE?

A

PGI2, PGE2

34
Q

What do eicosanoids act on?

A

G coupled receptors

35
Q

Which receptors do prostaglandins act on?

A

E4 receptors

E2 receptors are involved in bronchodilation
E3 receptors are involved inb ronchoconstriction

36
Q

What receptors do thromboxane act on?

A

TP receptors

37
Q

What does leukotriene B4 act on?

A

t BLT receptors

38
Q

What does LTB4 do?

A

leukotriene C4, D4, and E4 act onCys-LT receptors

LTB4 is chemotactic, leads to bronchoconstriction, increases vascular permeability, increases oedema, and increases secretion of thick viscous mucous

39
Q

Why shouldn’t you prescribe aspirin to someone with asthma?

A

since COX gets blocked by aspirin
arachidonic acid goes on to produce leukotrienes through the lipoxygenase pathway
bronchoconstriction

40
Q

What problems do Cys leukotrienes (LTC4, LTD4, LTE4) cause?

A

airway oedema, secretion of thick mucous, and smooth muscle contraction

41
Q

What are antagonists for the CysLT receptor?

A

Montelukast, pranlukast, and zileuton

42
Q

What do the CysLT receptor anatagonists help with?

A

prevention of mild to moderate asthma
early to late bronchoconstriction effects of allergens
exercise induced asthma and asthma provoked by NSAIDs (like aspirin)

43
Q

What are the effects of LTD4?

A

increased cellular infiltration of eosinophils and neutrophils
increased mucus secretion
increased bronchoconstriction
increased airway oedema

44
Q

What can bradykinin and serotonin activate?

A

thromboxane A2 in endothelial cells

45
Q

What can shear stress cause?

A

activate prostaglandin I2 in endothelial cells
this acts on IP receptor and cause vascular smooth muscle relaxation by increasing cAMP

prostaglandin I2 will also reduce platelet aggregation

46
Q

What does prostaglandin E2 act on?

A

E3 receptors on parietal cells in the stomach (these cells secrete HCl)= REDUCES HCL SECRETION

Prostaglandin E2 acts on E3 receptors on mucus secreting cells in the stomach = INCREASES ITS PRODUCTION

47
Q

What does fish oil contain?

A

eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that play significant roles in inflammation (anti inflam actions)

48
Q

What does poly unsaturated fatty oild (from fish) do?

A

reduces arachidonic acid
this leads to an increase in EPA and DHA in the body

lipoxygenase and cyclooxygenase enzymes now act on the EPA and DHA and produce structures that are slightly different to the normal PGs, TXs and LTs−there is lesser production of PGE3, TXB2, LTB4, 5-HETE, and LTE4

the consequence of this is as follows−there is an increase in production of LTB5, TXA3, LTE4, and 5HPETE in different structural forms-LTB5 is 10-100 times less chemotactic to neutrophils-ie it does not attract neutrophils

49
Q

What do E-series resolvins do?

A

E-series resolvins (resolvin D1-D4; EPA-derived mediators) have anti-inflammatory actions

50
Q

What do docosatrienes and neuroprotectins do?

A

Docosatrienes and neuroprotectins (D-series resolvins; DHA-derived mediators) have anti-inflammatory effects

WEEK 9 SEM 4 (9 decks)

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