eicosanoids in skin inflammation
TRANSCRIPT
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EICOSANOIDS IN SKIN
INFLAMMATION
Dr.Chandan PatilI MVSc V 1661/16Vety Pharmacology & ToxicologyDUVASU Mathura
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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,
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Cutaneous Eicosanoids Biosynthesis
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Cycloxygenase derieved mediators
• PGE2 is the main Cutaneous Eicosanoid produced by epidermal keratinocytes & dermal fibroblasts.
• PGE2 involved in Keratinocyte proliferation differentiation & modulation of dermal fibroblasts and facilitate in wound healing.
• PGE2 has direct effect on melanocyte mediated post inflamatory pigmentary response.
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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.
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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.
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Mechanism Of action• All Prostanoid receptors are G-Protein
Coupled receptors.• These prostanoids utilise IP3/DAG/CAMP
transducer mechanism to act on their receptors
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Eicosanoids in cutaneous inflammatory diseases
Atopic Dermatitis
Psoropsis Sunburn
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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.
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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
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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
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Sunburn Responce
• Characterised by increased COX and LOX mediated eicosanoid production
• UVR induced oxidative stress stimulates activity of PLA2 in human and animal skin
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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 .
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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
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