title: Leptin deficiency in mice counteracts imiquimod (IMQ)-induced psoriasis-like skin inflammation while leptin stimulation induces inflammation in human keratinocytes.
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.
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Theresa
authors.initials: T
authors.lastname: Stjernholm
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Ommen
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Ane
authors.initials: A
authors.lastname: Langkilde
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Johansen
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Iversen
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rosada
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Karin
authors.initials: K
authors.lastname: Stenderup
mesh_terms: D000634:Aminoquinolines; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D000077271:Imiquimod; D020381:Interleukin-17 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D020738:Leptin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011565:Psoriasis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D000097043:Interleukin-22
chemical_list: D000634:Aminoquinolines; D054418:Chemokine CCL20; D054360:Chemokine CXCL1; D000077271:Imiquimod; D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D020738:Leptin; D020780:Matrix Metalloproteinase 9; D012333:RNA, Messenger; D000097043:Interleukin-22; C108355:CCL20 protein, human; C493447:CCL20 protein, mouse; C475829:CXCL1 protein, human; C475895:Cxcl1 protein, mouse; C508600:IL6 protein, human; C098680:Il17a protein, mouse; C577686:interleukin-6, mouse; C579270:MMP9 protein, human
keywords: NHEKs; imiquimod; mouse model; ob/ob mice; psoriasis