Role Of The Dioxin Receptors (Aryl Hydrocarbon Receptors (AhR)) In The Induction of The Expression of The Matrix Metalloproteinase (MMP) – 1 Enzyme By Tobacco Smoke Extracts (For Professionals)

Role Of The Dioxin Receptors (Aryl Hydrocarbon Receptors (AhR)) In The Induction of The Expression of The Matrix Metalloproteinase (MMP) – 1  Enzyme By Tobacco Smoke Extracts (For Professionals)

Two types of aging:

• intrinsic aging
• extrinsic aging: ultraviolet and tobacco smoking

odds ratios for wrinkles in patients with risk factors versus no risk factor individuals

• sun exposure: 2.65
• smoking: 35 PA: 5.8
• age more than 80 years old: 7.5

Daniells score

4UPA=1 year’s wrinkles formation

Part 1

• The presenter did a study in Japanese and German women
• Japanese develop pigment spots and german develop wrinkles

Methodology:

• 53 German women and 18 Japanese women living in the region of Düsseldorf, Germany  aged 30 to70 years of age
• 48 Japanese women living in the region of Nagoya, Japan aged 30 to 70

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• -questionnaire: smoking, sunbed, living next to a road
• -skin ageing score
• -blood tests

Results:

• Japanese women have more pigment earlier and German women have more wrinkles at an earlier age
• Smoking increases spots back of hands in German women and wrinkles appear on the upper lip in Japanese women

Part 2

• Molecular changes (in fibroblasts)

Methodology:

• stimulation of cells with tobacco extracts and 30J/cm2 UVA
• collagen
• MMP and TIMPS (protéases inhibitors)

Results

• increase MMP
• collagen synthesis decreased
• tropoelastin
• proteoglycan accumulation
• reduced proteinases inhibitors)

Part 3

• Tobacco has 3800 constituents and include polycyclic aromatic hydrocarbons (PAH)
• AhR (Aryl hydrocarbon receptor):

1. located in the cytosol
2. lipophilic
3. links to UVB and xenobiotics (also known as dioxin receptor)
4. once linked to particles, translocated to the nucleus where it induces its effect (expression of CYp1A1…)

Study

Methodology:

• done on HaCaT, keratinocytes and fibroblasts with PCR expression (Polymerase Chain Reaction).

Results show that Hexane soluble extracts (Lipophilic) (and to PBS (Phosphate Buffer Saline) water soluble soluble):

• increases MMP1:
• reduces proteoglycans
• reduces procollagen (I and III)
• induces CYP1a1 (Cytochrome P1a1) and CyP1B1 expression (PCR)
• AHR is proven to be the obliged pathway because this response is abolished in AhR knockout mice

• Smoke extracts also induce 7-ethoxyresorufin-o-deethylaser activity (which is also abolished in AhR knockouts)

• Flavanoids 3-methoxy-4-nitroflavone and naphtoflavone blocks the induction of CYP1B1 and MMP-1.

Conclusion: the AhR pathway may be pathogenetically involved in extrinsic skin aging.

Contributors:

Dr Christophe HSU – dermatologist. Geneva, Switzerland

Morita A, Aging and Photoaging – 22nd World Congress of Dermatology (WCD) – Seoul, South Korea