Role Of Eicosanoids in skin inflammation and Effect of PUFA in its inflammation

1. EICOSANOIDS IN SKIN
INFLAMMATION
Dr.Chandan Patil
I MVSc V 1661/16
Vety Pharmacology & Toxicology
DUVASU Mathura

2. INTRODUCTION
• Eicosanoids are major group of lipid –derieved
autacoids.
• Primarily derieved from Arachidonic acid
• Contribute to number of physiological and
pathological processes I,e homeoststic processes
and inflammatory responces.
• Eiconoid group includes
Prostaglandins,Thromboxanes,Leukotriens etc,

3. Cutaneous Eicosanoids
Biosynthesis

4. Cycloxygenase derieved mediators
• PGE2 is the main Cutaneous Eicosanoid
produced by epidermal keratinocytes & dermal
fibroblasts.
• PGE2 involvedin Keratinocyte proliferation
differentiation & modulation of dermal
fibroblasts and facilitate in wound healing.
• PGE2 has direct effect on melanocyte mediated
post inflamatory pigmentary response.

5. Cycloxygenase derieved mediators cont…
• Cutaneous PGD2 are produced by Langerhans
cells and Dermal mast cells
• Cutaneous PGD2 is a potent anti-proliferative
and anti-inflammatory PG
• PGD2 is precussor to the anti-inflammatory
cyclopentanone prostaglandins:PGJ2 that are
formed through non enzymatic hydrolysis.

6. Lipoxygenase derieved mediators
• Skin express 5-,8-,12-,15-LOX activity to produce
Hydroxyeicosatetraenoic acid(HETE) from fatty
acid derivatives of AA, Linoleic acid etc.
• 12HETE is potent pro-inflammatory chemotactic
mediator produced by epidermal keratinocytes &
dermal fibroblasts.
• 12 HETE binding sites are expressed by
keratinocytes and langerhans cells suggesting
active involvement in cutaneous wound healing
and inflammatory diseases.

7. Mechanism Of action
• All Prostanoid receptors are G-Protein
Coupled receptors.
• These prostanoids utilise IP3/DAG/CAMP
transducer mechanism to act on their receptors

8. Eicosanoids in cutaneous
inflammatory diseases
Atopic Dermatitis
Psoropsis Sunburn

9. Psoriasis
• Chronic inflammatory & proliferative skin
disease with genetic and environmental
etiologies characterised by abnormalities in
skin lipids and increased production of
inflammatory mediators
• Studies shown there is increased PLA2 activity
& high concentration of 12-HETE which is a
potent chemotactic eicosanoid highly prevalent
in psoriatic skin.

10. Psoriasis cont…
• On repeated injection of 15-HETE synthesised
by 15-LOX on the Psoriactic plaques resulted
in regression and complete resolution of
psoriasis
• So there has been interest in developing
specific 12-LOX & PLA2 inhibitors as
theraupetic agents to treat psoriasis

11. Atopic Dermatitis
• Characterised by increased PLA2 activity with
COX derieved prostanoids mediators.
• PGD2 is the principle prostanoid involved
because of active role of langerhans cells and
mast cells.
• Invitro studies with GLA and DHA suggested
PUFA can alter eicosanoids produced by
immune cells which helps in treating atopic
dermatitis

12. Sunburn Responce
• Characterised by increased COX and LOX
mediated eicosanoid production
• UVR induced oxidative stress stimulates
activity of PLA2 in human and animal skin

13. Effect of PUFA in Cutaneous
inflammation
• Long chain n-3PUFA effect eicosanoid production
through their ability to offer alternative substrates to
lipid metabolizing enzymes.
• Fish derieved omega-3 fatty acid
EPA(eicosapentaenoic acid) on action by COX
produce PGE3 which is less inflammaory & 12 lox
product such as 12-HEPE is less potent
chemoattractant than their Arachidonic acid
counterpart
• EPA also inhibit s COX2 expression in many cell
types .

15. References
• Eicosanoids in skin inflammation review article by Anna Nicolaou from
www.elsevier.com/plefa
• REDUCING INFLAMMATION WITH DIET AND SUPPLEMENTS:The Story of
Eicosanoid Inhibition general review by Subhuti Dharmananda, Ph.D.,
Director, Institute for Traditional Medicine, Portland, Oregon