Question 1

You are studying the effects of a previously uncharacterized drug upon oral administration to experimental animals. Your tests involve examination of the effects of this compound within the gut following inducement of colitis-like symptoms. You find that administration of the drug to these animals leads to a reduction in the severity of inflammation in the gut and enhances a return to normal GI activity. Your test compound is most likely inducing the synthesis of which of the following compound?

A) LTB₄
B) LXA₄
C) PCI₂
D) PGE₂
E) TXA₂

Accepted Answer

Lipoxin A4 (LXA4) is known for its anti-inflammatory properties and ability to promote the resolution of inflammation, which aligns with the observed effects of the drug in reducing gut inflammation and restoring normal gastrointestinal activity.

Question 2

A defect in which of the following enzyme activities would impair the production of the lipoxins by the classic pathway (ie, nonaspirin triggered) in neutrophils?&#10;A) COX-1&#10;B) COX-2&#10;C) 5-LOX&#10;D) 12-LOX&#10;E) 15-LOX

Accepted Answer

5-LOX (5-lipoxygenase) is crucial for the initial steps in the production of leukotrienes and lipoxins. A defect in 5-LOX would impair the production of lipoxins in the classic pathway. In one of the classical pathways of lipoxin synthesis, the interactions between epithelial cells and neutrophils require the activities of both 15-LOX and 5-LOX. Within the epithelial cells, the PLA₂-mediated release of arachidonic acid serves as a substrate for 15-LOX and generates 15S-H(p)ETE. This latter compound will then diffuse out of the epithelial cells and be taken up by neutrophils where the activity of 5-LOX will then convert it into 15S-epoxytetraene, which is the precursor for LXA₄ synthesis

Question 3

The lipoxins are characterized as pro-resolving compounds because they promote the resolution of an inflammatory response. Which of the following activities is associated with this pro-resolution function?

A) activation of TNF-α secretion
B) inhibition of polymorphonuclear (PMN) cell apoptosis
C) inhibition of the action of TGF-β
D) reduction in neutrophil infiltration at the site of inflammation
E) stimulation of IL-8 release

reduction in neutrophil infiltration at the site of inflammation

Accepted Answer

Lipoxins are involved in resolving inflammation by reducing neutrophil infiltration at the site of inflammation, thus promoting the resolution phase of the inflammatory response.  Lipoxins and epi-lipoxins inhibit neutrophils (PMN) chemotaxis, PMN-mediated increases in vasopermeability, and PMN adhesion and migration through the endothelium. Additional anti-inflammatory actions of the lipoxins and aspirin-triggered lipoxins include blocking expression of the IL-8 gene (a pro-inflammatory chemokine produced by macrophages and endothelial cells, which stimulates neutrophil migration), inhibition of the release and actions of TNF-α, and stimulation of TGF-β activity.

Question 4

You are studying the responses of renal tissue to
Ischemic injury in laboratory animals. You find
That in these animals there is an initial inflammatory response detectable within the renal tissue,
But it does not normally abate as expected; it only
Worsens resulting in total renal failure. Measurements of enzyme activities in renal tubule cells indicate that PLA₂ and COX-2 are functional. The lack of synthesis of which of the following lipid mediators is the most likely cause of the failure to limit the inflammatory responses in this animal model?

A) LTB₄
B) PD₁
C) PGE₂
D) RvD1
E) TXA₂

Accepted Answer

The answer of You are studying the responses of renal...

Question 5

You are examining the lipid synthesis characteristics of mixed cell types in culture. You find that the cells normally activate PLA2 and that you can detect the synthesis of the intermediate 15S-H(p) ETE. However, in this system you cannot detect the subsequent production of LXA4. Which of the following enzymes is most likely not functional in this culture system?

A) COX-1
B) COX-2
C) 5-LOX
D) 12-LOX
E) 15-LOX

Accepted Answer

5-LOX is the enzyme that is responsible for the synthesis of LXA4. Since LXA4 is not being produced in this system, it is likely that 5-LOX is not functional. In one of the classical pathways of lipoxin synthesis the interactions between epithelial cells and leukocytes requires the activities of both 15-LOX and 5-LOX. Within the epithelial cells, the PLA₂-mediated release of arachidonic acid serves as a substrate for 15-LOX and generates 15S-H(p) ETE. This latter compound will then diffuse out of the epithelial cells and be taken up by leukocytes where the activity of 5-LOX will then convert it into 15S-epoxytetraene, which is the precursor for LXA₄ synthesis. Therefore, the presence of upstream activities and lipid products in the absence of LXA₄ synthesis indicates that there is a defect in the activity of 5-LOX in this system.

Question 6

Aspirin exerts several beneficial effects within the vasculature that result in protection against intravascular inflammation and resultant atherosclerosis. These actions of aspirin involve, in part, its ability to modify the activity of lipid-synthetic enzymes. Which of the following enzymes is a target for aspirin-mediated modification resulting in an altered activity?

A) COX-2
B) D5-desaturase
C) 5-LOX
D) prostacyclin synthase
E) thromboxane synthase

Accepted Answer

Aspirin primarily targets and acetylates the enzyme cyclooxygenase (COX), specifically COX-1 and COX-2, leading to the inhibition of prostaglandin synthesis, which plays a role in inflammation and atherosclerosis. Aspirin-induced acetylation of COX-2 alters the enzyme such that it converts arachidonic acid to 15R-hydroxyeicosatetraenoic acid (15R-HETE) instead of into prostaglandin H2 (PGH₂). 15R-HETE is then rapidly metabolized to the epi-lipoxins in monocytes and leukocytes through the action of 5-lipoxygenase (5-LOX).

Deck 24: Lipids: Lipid Mediators of Inflammation