Prostaglandin E2, mast cells and asthma

In the mast cell community, we talk about prostaglandins a lot. Most of the time we are talking about prostaglandin D2, as it is well produced by mast cells. However, there are a number of other prostaglandins that can affect inflammation and disease processes.

Prostaglandin E2 has been inflammatory and anti-inflammatory effects in the body. It is the prostaglandin responsible for inducing fevers. It is also a vasodilator, which contributes in some models to swelling. It relaxes smooth muscle and interferes with release of norepinephrine. PGE2 can cause hyperalgesia, or exaggerated pain response, a hallmark of inflammation. It regulates blood pressure, body temperature, sleep-wake pattern, kidney function and peristalsis (movement through the GI tract), and intestinal secretion.

It activates T cells and favors development of certain types of T cells that participate in the allergic response. It also modulates B cell activity and allergic reactions. However, it makes other immune cells less active. PGE2 simulates bone resorption and is important in reproduction, softening the cervix and causing uterine contractions.

PGE2 has a number of interactions with mast cells. In mast cells from bone marrow or peritoneal cavity, it induces histamine, IL-6 and GM-CSF release. However, in mast cells from progenitor cells or in the lung, it decreases release of leukotrienes, TNF and histamine. PGE2 acts on mast cells to reduce expression of PGE receptors, EP2 and EP3. PGE2 can enhance IgE production by B cells but also interferes directly with mast cell degranulation stimulated by IgE.

Prostaglandin E2 has a very unusual relationship with allergic inflammation. In contrast to prostaglandin D2, which constricts the airway, PGE2 actually relaxes the smooth muscle and opens the airway. Importantly, PGE2 retains this ability regardless of the trigger for reactive airway – allergen, asthma or exercise. Curiously, it was observed early on to cause coughing.

An interesting fact is that administration of medications that interfere with COX-2 (like Celebrex or aspirin) can worsen airway function and increase inflammation. This is of particular note in asthma patients. It is thought that this may be due to reducing production of PGE2.

 

References:

Emanuela Ricciotti, Garret A. FitzGerald. Prostaglandins and Inflammation. Arterioscler Thromb Vasc Biol. 2011; 31: 986-1000.

Rosa Torres, César Picado, Fernando de Mora. The PGE2–EP2–mast cell axis: An antiasthma mechanism. Molecular Immunology 63 (2015) 61–68

Daniel F. Legler, Markus Bruckner, Edith Uetz-von Allmen, Petra Krause. Prostaglandin E2 at new glance: Novel insights in functional diversity offer therapeutic chances. The International Journal of Biochemistry & Cell Biology 42 (2010) 198–201.