CHART of specific / significant eicosanoids and their effects

To learn the basics of eicosanoids:

"Local Hormones" (Eicosanoids) - Cell's "First Response" team -  Mediators of inflammation / pain, blood pressure, blood clotting, tissue repair . . .

Meet the VIP eicosanoid families and their members

Or ... Go straight to the eicosanoid chart

To help understand the effects of eicosanoids, this website color-codes their families and their members by their overall function.  Their activities can not be differentiated as "good" and "bad".   E.g. promoting inflammation is very necessary to aid repair, if say you've been injured, but can be overly painful and damage tissue if done to excess, or causing the blood to clot can be life-saving if you just cut yourself, but can cause a heart attack if overdone in the arteries, and lastly, cell-proliferation is needed to repair tissue, but when out of control can cause a tumor. Excessive or unresolved inflammation, or overreaction to stimuli can lead to uncontrolled tissue damage and health problems. 

 "Orange"  represents activity altering the status quo, some increasing inflammation.

 "Turqoise" represents more of a "calming down" / going-back-to-normal action and/or resolving the inflammation.

 "Red"  represents generally inflammatory activity.

 "Green"  represents generally anti-inflammatory activity.

The eicosanoid families

•   The PROSTAGLANDIN family (a prostanoid):  Produced in most cells;

Series 1 (PGE1) and Series 3 prostaglandins. Counter inflammation

Series 2 prostaglandins.   Significant ones are PGD2, PGE2, PGF2α, PGI2 (a.k.a. prostacyclin. a potent vasodilator produced mainly by endothelial cells, which comprise the inner lining of blood and lymphatic vessels, and epithelial cells lining the inside of other hollow organs e.g. bronchial epithelial cells in airways, and the skin's epidermis.

•   The THROMBOXANE family (a prostanoid):   Produced mainly in platelets, also placenta, lungs;

 Mainly thromboxane TXA2. Promotes blood clotting /platelet-aggregation and is a potent vasoconstrictor. Also broncho-constrictive.

•  The LEUKOTRIENE family:  Produced in leukocytes.  i.e. white blood cells:  Series 4 and Series 5 leukotrienes

•  The EOXIN family:  Produced in immune system eosinophils (white blood cells), mast cells, and some other tissues. Generally steps up inflammatory response.

•  The LIPOXIN and RESOLVIN families: Deal with reducing excessive tissue injury and  the resolution of inflammation.

 LIPOXINS ( Produced in platelets, neutrophils, red blood cells and reticulocytes; also by low dose aspirin).

RESOLVINS (Produced in most cells) Potent anti-inflammatory agents that as their name suggests,  resolve inflammation. They limit the extent of inflammation by blocking the actions of inflammatory prostanoids (prostaglandins and thromboxanes) and also clear away breakdown products of inflammation process. E.g. RVD1-6

•  The PROTECTIN family 

Eicosanoid activity is complex

Each family member has specific functions.   However, their activity can be confusing, since their tissue location, and which enzyme produced them can sometimes determine whether they either promote or resolve inflammation.

Dietary omega-3 EPA and omega-6 GLA counter the predominately inflammatory effects of omega-6 AA in three ways:

•   Competitive inhibition.   DGLA and EPA compete with AA for COX and LOX enzymes, such that the presence of DGLA and also EPA in tissues lowers the production of AA's eicosanoids

•   Displacement.   Increased dietary omega-3 results in decreased AA in brain and other tissue.  Green et al, 2005

•   Direct counteraction.   Some DGLA and EPA-derived eicosanoids counteract their AA derived counterparts.   E.g.  PGE1 derived from DGLA acts against PGE2 derived from AA.

COX enzymes

 COX-1 - "The housekeeper"

 COX-1 is expressed constitutively in most tissues and regulates basal levels of prostaglandins to maintain general homeostasis.   Only COX-1 produces prostaglandins that protect the stomach and intestinal lining.

 COX-1 is also actively involved in certain  traumatic/stimulated events.    Only COX-1 produces prostaglandins that activate platelets and constrict airways.

The human COX-1 gene is located on chromosome 9

 COX-2 - "The main activator"

COX-2 enzyme is mostly induced in "times of trouble".  Responsible for releasing PROSTAGLANDINS after an infection, injury, or in cancer development, COX-2 expression is induced by the cytokines interleukin (IL)-1, IL-2, and TNF, as well as by lipopolysaccharide (LPS) produced by Gram-negative bacteria.  Kang et al, 2007

COX-2 enzyme inhibitors reduce the prostanoids PGI2, PGD2, PGE2 PGF2α, and thromboxane A2

The human COX-2 gene is located on chromosome 1

Traditional NSAIDs (e.g. aspirin, Aleve, Motrin) suppress both COX-1 and COX-2 enzymes

NSAIDS (Cox enzyme inhibitors / Coxibs) - Anti-inflammatory drugs WARNING!

Chart of significant eicosanoids and their effects (Currently adding to this list)
Prostanoids: Prostaglandins (produced in most cells)  and Thromboxanes via COX-1 (housekeeping) and COX-2 (mostly induced under stress conditions) enzymes
PGE1  Derived directly from: Omega-6 DGLA (in mother's milk). Derived indirectly with the sufficient presence of omega-3 EPA from: Omega-6 LA (E.g. in nuts, seeds, vegetable oils, grass-fed animal fats or legumes,  or from GLA (E.g. in borage /evening primrose oil),
Released area	Action	Information
All cells	Counters inflammation Reduces pain	Sesame lignans promote conversion of omega-6 DGLA to anti-inflammatory PGE1 in favor of pro-inflammatory omega-6 AA
Blood vessels	Vasodilation Normalize BP
Immune System cells	Enhance immune response
Bronchial airways	Bronchodilation
PGD2 Derived from omega-6 AA mostly (in the Western diet) from meat and eggs; inhibited by omega-3 EPA presence;
PGD2 is a major prostaglandin produced by immune system (IS) mast cells (contain histamine and the anticoagulant heparin).   Recruits T-helper (CD4) cells (important in adaptive IS), eosinophils (a type of white blood cell (WBC) that aids IS combat against multicellular parasites and other infections), basophils (another WBC granulocyte responsible for inflammatory reactions during an immune response, and in the formation of acute and chronic allergic diseases).
Released area	Action	Information
Mast cells in Airways; Macrophages;	Potent bronchoconstrictor	Involved in allergic rhinitis and allergic bronchial asthma. Atttracts neutrophils (WBCs that fight infection and heal injuries). Involved in late phase reactions to allergens (6 hrs after exposure).  PGD2 has 10 times higher concentration in asthma patients compared to control patients.
Mast cells in PULMONARY and PLACENTAL blood vessels	Potent vasoconstrictor	PGD2 is a potent vasoconstrictor via thromboxane/endoperoxide (TX/E) receptor activation in pulmonary vessels, but this mechanism is not responsible for vasoconstriction in systemic vessels or in airway. King, 1991
Mast cells in UTERINE blood vessels	Vasodilation	PGD2 can promote mild vasodilation if TX/E is blocked.  King, 1991 PGD2 dilates uterine blood vessels. Together with its ability to constrict placental blood vessels, it may control utero-placental blood flow.
Mast cells in brain		In mamalian organs, large amounts of PGD2 are found only in the brain (and in mast cells)
Mast cells in skin	Vasodilation	PGD2 is the primary mediator of vasodilation after taking niacin (vitamin B3) - the so-called "niacin flush". Involved in urticuria (hives), and balding - a causal link was found between elevated levels of localized PGD2 and hair growth inhibition (by increasing Prostaglandin D2 synthase). Garza et al, 2012.
PGE2 Derived from omega-6 AA mostly (in the Western diet) from meat and eggs; inhibited by omega-3 EPA presence;
PGE2 promotes tumor growth.   PGE2 is the most abundant prostaglandin found in various human malignancies, including colon, lung, breast, and head and neck cancer, also often associated with a poor prognosis.  In contrast, the enzyme that catalyzes the degradation of PGE2 (15-PGDH, an antagonist /suppressor of COX-2) is highly expressed in normal tissues but is ubiquitously lacking in human colon, gastric, lung and breast cancer. Lack of 15-PGDH expression in these tumours results in increased endogenous PGE2 levels. Furthermore there may be a negative feedback loop, since a product of the COX-2 enzymatic pathway, upregulates the expression of 15-PGDH in breast cancer MDA-MD-231 cells. 15-PGDH is being investigated as a potential avenue for tissue regeneration. PubMed.  Prostaglandin E Synthase (PGES) converts PGH to PGE.  COX-1 inhibits PGE2 synthesis
Released area	Action	Information
Brain ; Joints;  via Cox-2	Inflammation /Pain	Promotes all signs of classic inflammation: i.e. redness, swelling and pain. Redness and edema result from increased blood flow into the inflamed tissue through PGE2-mediated increase in arterial dilation and microvascular permeability. Pain results from the action of PGE2 on peripheral sensory neurons and on central sites within the spinal cord and the brain  Quercetin reduces PGE2 (RA joints Link)
Airways	Bronchodilating
Vascular SMCs (in arteries, veins, lymphatic vessels); SMCs are also in walls of stomach, intestine and bladder, and other hollow organs;	Vasodilating	Dilates smooth muscles cells (SMCs), which form the supporting tissue of blood vessels and hollow internal organs (e.g. stomach, intestine, and bladder)
	Normalize BP
Platelets
Gastric mucosa via Cox1		Protects stomach lining; 🠡 mucous /bicarbonate secretion; 🠡 mucosa blood flow; 🠣 gastric acid /PEPSIN secretion; Provides gastrointestinal integrity (Cox-2?) 🠡 duodenal mucus secretion
Kidneys
		Involved in fertility
		Regulates immune responses;
PGF2α  (Derived via Cox1, Cox2 from omega-6 AA  (in the Western diet, this is mostly from meat (especially chicken) and eggs); inhibited by omega-3 EPA presence;
Released area	Action	Information
Airways	Bronchoconstricting	Anomaly: Promoted by Cox1 inhibitors (aspirin, traditional NSAIDs) Harrington, 2008
Vascular Smooth Muscle Cells (VSMCs) via Cox2	Vasoconstricting Raise BP
Uterus; Bladder	Contraction
Eyes
PGI2 (Prostacyclin) (Derived from AA via Cox1, Cox2)
Released area	Action	Information
Endothelial  cells lining inside of blood and lymphatic vessels  (epithelial cells lining hollow  organs, airways, gastrointestinal lining, skin) via Cox-1 and Cox-2	Vasodilating	PGI2 has a beneficial effect on allergic airway responses and pulmonary hypertension. e.g. in asthma. Zhou, 2016
	Normalize BP
Airways	Bronchodilating
Platelets via Cox1 and Cox2)	PGI2 Inhibits clot formation
Kidney
Gastric mucosa via Cox1	Protects stomach lining
TXA2 Thromboxane (TXA2-->TXB2) (from AA e.g. meat, eggs, or indirectly from LA in seed oils)
Released area	Action	Information
Vascular Smooth Muscle Cells (VSMCs) via Cox2	Vasoconstricting
	Raise BP
	VSMC proliferation	Cell proliferation aids damage repair. Involved in development of atherosclerosis;
Platelets; via Cox1	Blood clotting	Involved in thrombosis
Airways	Bronchoconstricting	An anomaly is that bronchoconstriction is promoted by Cox-1 inhibitors (aspirin, traditional NSAIDs), but not selective Cox-2 inhibitors Harrington, 2008
Placenta
KIdney
Macrophages
Series 3 PGs Derived from  omega-3 EPA  e.g. in salmon, salmon, fish, cod liver or  krill oil
Released area	Action	Information
Most cells via Cox1 and Cox 2	Counters inflammation	COUNTER  PG-2s,  LT-4s Compete for COX and LOX enzymes
Leukotrienes
Series 4 LTs Derived from AA e.g. meat, eggs, or indirectly from LA in seed oils
Released area	Action	Information
Mast cells (concurrent release with histamine) via 5-LO	Bronchoconstricting	Part of the inflammation response, especially in asthma and allergic rhinitis. Attract white blood cells to sites of tissue damage and cause smooth muscles to contract.
Series 5 LTs Derived from omega-3 EPA e.g. in fish oil
Released area	Action	Information
Mast cells via  5-LO	Counters inflammation
Specialized pro-resolving mediators (SPMs Deal with  reducing excessive tissue injury and resolving inflammation.
Lipoxins
Released area	Action	Information
Low dose aspirin can trigger lipoxin synthesis
Platelets via 12-LO From LTA5
Neutrophils via 15-LO From AA
Erythrocytes, Reticulocytes via 12-LO From AA
Resolvins (RVs) (from EPA, DHA, DPA e.g. fish oil)
Released area	Action	Information
	Newly discovered resolvins are anti-inflammatory and inflammation resolving.	Clear away inflammation debris Block prostanoid effects
Protectins (PDs) from O3
Released area	Action	Information
Eoxins
Eoxins (EX) (from AA e.g. meat, eggs, or indirectly from LA in seed oils)
Released area	Action	Information
Eosinophils  (white blood cells), mast cells via LOX		Involved in asthma,  lymphoma of Hodgkins disease, prostate cancer, colon cancer, and other cancers

References

Garza, Luis A.; et al. (2012, Mar 12).  "Prostaglandin D Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia". Science Translational Medicine. 4 (126): 126ra34. PubMed

Green, P., Gispan-Herman, I., & Yadid, G. (2005). Increased arachidonic acid concentration in the brain of Flinders Sensitive Line rats, an animal model of depression. Journal of lipid research, 46(6), 1093-1096. PubMed