Journal ArticleDOI
Leptin deficiency in mice counteracts imiquimod (IMQ)-induced psoriasis-like skin inflammation while leptin stimulation induces inflammation in human keratinocytes
Theresa Stjernholm,Pernille Ommen,Ane Langkilde,Claus Johansen,Lars Iversen,Cecilia Rosada,Karin Stenderup +6 more
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TLDR
Leptin deficiency attenuated IMQ‐induced psoriasis‐like skin inflammation in a mouse model, and leptin stimulation induced a pro‐inflammatory phenotype in human keratinocytes, thus, supporting an aggravating role of leptin in Psoriasis.Abstract:
Leptin is an adipocyte-derived cytokine secreted mostly by adipose tissue. Serum leptin levels are elevated in obese individuals and correlate positively with body mass index (BMI). Interestingly, serum leptin levels are also elevated in patients with psoriasis and correlate positively with disease severity. Psoriasis is associated with obesity; patients with psoriasis have a higher incidence of obesity, and obese individuals have a higher risk of developing psoriasis. Additionally, obese patients with psoriasis experience a more severe degree of psoriasis. In this study, we hypothesised that leptin may link psoriasis and obesity and plays an aggravating role in psoriasis. To investigate leptin's role in psoriasis, we applied the widely accepted imiquimod (IMQ)-induced psoriasis-like skin inflammation mouse model on leptin-deficient (ob/ob) mice and evaluated psoriasis severity. Moreover, we stimulated human keratinocytes with leptin and investigated the effect on proliferation and expression of pro-inflammatory proteins. In ob/ob mice, clinical signs of erythema, infiltration and scales in dorsal skin and inflammation in ear skin, as measured by ear thickness, were attenuated and compared with wt mice. Moreover, IL-17A and IL-22 mRNA expression levels, as well as increased epidermal thickness, were significantly less induced. In vitro, the effect of leptin stimulation on human keratinocytes demonstrated increased proliferation and induced secretion of several pro-inflammatory proteins; two hallmarks of psoriasis. In conclusion, leptin deficiency attenuated IMQ-induced psoriasis-like skin inflammation in a mouse model, and leptin stimulation induced a pro-inflammatory phenotype in human keratinocytes, thus, supporting an aggravating role of leptin in psoriasis.read more
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Journal Article
Cell-mediated immunity in genetically obese (C57Bl/6J ob/ob) mice.
TL;DR: Cytotoxic response of spleen cells of obese mice immunized in vivo was markedly lower than that of lean controls, whereas the generation of T killer cells against alloantigens after in vitro immunization was unimpaired, which points to a deleterious "microenvironment" in obesity.
Journal ArticleDOI
Psoriasis and Cardiovascular Comorbidities: Focusing on Severe Vascular Events, Cardiovascular Risk Factors and Implications for Treatment
TL;DR: The evidence regarding the association between psoriasis and cardiovascular comorbidities is reviewed, focusing on severe vascular events, cardiovascular risk factors and implications for treatment.
Journal ArticleDOI
Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study
Ashley Budu-Aggrey,Ben Michael Brumpton,Jess Tyrrell,Jess Tyrrell,Sarah H Watkins,Ellen Heilmann Modalsli,Carlos Celis-Morales,Lyn D. Ferguson,Gunnhild Åberge Vie,Tom Palmer,Lars G. Fritsche,Mari Løset,Jonas B. Nielsen,Wei Zhou,Lam C. Tsoi,Andrew R. Wood,Samuel E. Jones,Robin N Beaumont,Marit Saunes,Pål Richard Romundstad,Stefan Siebert,Iain B. McInnes,James T. Elder,James T. Elder,George Davey Smith,Timothy M. Frayling,Bjørn Olav Åsvold,Sara J. Brown,Sara J. Brown,Naveed Sattar,Lavinia Paternoster +30 more
TL;DR: Evidence that higher BMI leads to a higher risk of psoriasis is provided, which supports the prioritization of therapies and lifestyle interventions aimed at controlling weight for the prevention or treatment of this common skin disease.
Journal ArticleDOI
New insights into different adipokines in linking the pathophysiology of obesity and psoriasis.
TL;DR: Evidence is provided which identifies a potential therapeutic target aiming at adipokines for the management of these two diseases, and the potential mechanisms whereby different adipokine link obesity and psoriasis are summarized.
Journal ArticleDOI
Body mass index, abdominal fatness, weight gain and the risk of psoriasis: a systematic review and dose–response meta-analysis of prospective studies
TL;DR: A systematic review and dose–response meta-analysis of different adiposity measures and the risk of psoriasis to provide a more robust summary of the evidence based on data from prospective studies found that adiposity as measured by BMI, waist circumference, waist-to-hip ratio, and weight gain is associated with increased risk of Psoriasis.
References
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Journal ArticleDOI
Positional cloning of the mouse obese gene and its human homologue
Yiying Zhang,Ricardo Proenca,Ricardo Proenca,Margherita Maffei,Marisa Barone,Marisa Barone,Lori Leopold,Lori Leopold,Jeffrey M. Friedman,Jeffrey M. Friedman +9 more
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Journal ArticleDOI
Role of leptin in the neuroendocrine response to fasting
Rexford S. Ahima,Daniel Prabakaran,Christos S. Mantzoros,Daqing Qu,Bradford B. Lowell,Eleftheria Maratos-Flier,Jeffrey S. Flier +6 more
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Journal ArticleDOI
Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides
Spencer Liang,Xiang-Yang Tan,Deborah Luxenberg,Riyez Karim,Kyriaki Dunussi-Joannopoulos,Mary Collins,Lynette A. Fouser +6 more
TL;DR: IL-22 is identified as a new cytokine expressed by Th17 cells that synergizes with IL- 17A or IL-17F to regulate genes associated with skin innate immunity.
Journal ArticleDOI
Mechanisms of Disease: Psoriasis.
TL;DR: Anti-TNF strategies have three variants: a humanized chimeric anti–TNF- α monoclonal antibody, a fully human monocolonal anti-T NF- α antibody, and a human p75 TNF-receptor Fc fusion protein.
Journal ArticleDOI
Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis
Leslie van der Fits,Sabine Mourits,Jane S. A. Voerman,Marius Kant,Louis Boon,Jon D. Laman,Ferry Cornelissen,Anne-Marie Mus,Edwin Florencia,Errol P. Prens,Erik Lubberts +10 more
TL;DR: The sole application of the innate TLR7/8 ligand IMQ rapidly induces a dermatitis closely resembling human psoriasis, critically dependent on the IL-23/IL-17 axis.
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