Obesity exacerbates imiquimod-induced psoriasis-like epidermal hyperplasia and interleukin-17 and interleukin-22 production in mice.

Abstract

Psoriasis is a chronic inflammatory skin disorder that is accompanied by an imbalance between the proliferation and differentiation of keratinocytes. A number of studies have suggested an association between obesity and severe psoriasis; however, it remains to be clarified whether obesity exacerbates psoriasis. To address this unsolved question, we induced psoriasiform dermatitis in mouse models for obesity. We found that obesity exaggerated the severity of psoriasiform dermatitis induced by topical application of the Toll-like receptor (TLR) 7 agonist, imiquimod. Ear swelling and epidermal hyperplasia were more prominent in the obese mice than in the control mice. When compared to imiquimod-treated control mice, imiquimod-treated obese mice expressed higher levels of psoriasis mediators, interleukin-17A (IL-17A) and IL-22 in the skin. Food intake restriction partially abrogated enhanced ear swelling and cytokine overproduction in obese mice. Furthermore, the obesity environment and imiquimod treatment synergistically induced an IL-17A downstream molecule, regenerating islet-derived 3γ (Reg3γ), which is a critical molecule for psoriatic epidermal hyperplasia. Palmitic acid, one of the fatty acids released by subcutaneous adipocytes, increased the expression of REG3A (a human homologue of mouse Reg3γ) in both the HaCaT keratinocyte cell line and normal human keratinocytes. Taken together, these results strongly suggest that obesity exacerbates psoriasiform dermatitis in mice by upregulating IL-17A, IL-22 and Reg3γ.

• Authors: Kaori Kanemaru, Ayano Matsuyuki, Yoshikazu Nakamura, Kiyoko Fukami
• Journal: Experimental dermatology (Exp Dermatol) Vol. 24 Issue 6 Pg. 436-42 (Jun 2015) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 25777289 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Aminoquinolines
• Interleukin-17
• Interleukins
• Membrane Glycoproteins
• Pancreatitis-Associated Proteins
• Proteins
• REG3A protein, human
• Reg3g protein, mouse
• Tlr7 protein, mouse
• Toll-Like Receptor 7
• Phosphatidylinositol 3-Kinases
• Imiquimod

Topics

• Aminoquinolines (adverse effects, pharmacology)
• Animals
• Cell Line
• Disease Models, Animal
• Epidermis (drug effects, metabolism, pathology)
• Female
• Humans
• Hyperplasia
• Imiquimod
• Interleukin-17 (metabolism)
• Interleukins (metabolism)
• Keratinocytes (drug effects, metabolism, pathology)
• Male
• Membrane Glycoproteins (agonists)
• Mice
• Mice, Mutant Strains
• Obesity (complications)
• Pancreatitis-Associated Proteins
• Phosphatidylinositol 3-Kinases (metabolism)
• Proteins (metabolism)
• Psoriasis (chemically induced, metabolism, pathology)
• Toll-Like Receptor 7 (agonists)
• Interleukin-22