Sun exposure and PDZK1 genotype modulate PDZK1 gene expression in normal skin

Human skin pigmentation results from the enzymatically controlled synthesis of melanin pigments in specialized organelles (melano‐somes) produced within epidermal melanocytes, followed by their transfer to neighboring keratinocytes and their distribution through‐out the epidermis.1 Constitutive skin pigmentation seems to be mostly genetically determined,2 being altered by numerous intrinsic and extrinsic factors affecting the epidermal melanin unit

Adenosine A2A and A2B Receptors Differentially Modulate Keratinocyte Proliferation: Possible Deregulation in Psoriatic Epidermis

Adenosine is a potent regulator of inflammation and immunity, but the role of adenosine receptors in keratinocytes remains controversial. We determined that in addition to A2B receptors, human epidermal keratinocytes also express A2A receptors, although to a lower extent. Through the use of selective adenosine receptor agonists and antagonists, we showed that physiological concentrations of adenosine activate A2B receptors in normal human keratinocytes, inducing cell cycle arrest through the increase of intracellular calcium but not through cAMP signaling. In contrast, the selective activation of A2A receptors by CGS-21680 induces keratinocyte proliferation via p38–mitogen-activated protein…

Decreased SAPK/JNK signalling affects cytokine release and STAT3 activation in psoriatic fibroblasts.

Topical application of the adenosine A2Areceptor agonist CGS-21680 prevents phorbol-induced epidermal hyperplasia and inflammation in mice

The nucleoside adenosine is a known regulator of immunity and inflammation that mediates, at least in part, the anti-inflammatory effect of methotrexate, an immunosuppressive agent widely used to treat autoimmune inflammatory diseases. Adenosine A2A receptors play a key role in the inhibition of the inflammatory process besides promoting wound healing. Therefore, we aimed to determine the topical effect of a selective agonist, CGS-21680, on a murine model of skin hyperplasia with a marked inflammatory component. Pretreatment with either CGS-21680 (5 μg per site) or the reference agent dexamethasone (200 μg/site) prevented the epidermal hyperplasia and inflammatory response induced by topica…

Defective Induction of COX-2 Expression by Psoriatic Fibroblasts Promotes Pro-inflammatory Activation of Macrophages

Fibroblasts play an important role as members of the innate immune system through the secretion of COX-2-derived inflammatory mediators such as prostaglandin E-2 (PGE(2)). However, it has been described that dermal fibroblasts behave like mesenchymal stem cells reducing lymphocyte recruitment and dendritic cell activation through PGE(2) release. As the role of fibroblasts in psoriasis remains poorly characterized, in the present study we have evaluated the possible influence of PGE(2) derived from dermal fibroblasts as modulator of the immune response in psoriatic skin. Our results indicate that under inflammatory conditions, psoriatic fibroblasts showed defective induction of COX-2, which …

Improved effectiveness from individualized dosing of self-administered biologics for the treatment of moderate-to-severe psoriasis: a 5-year retrospective chart review from a Spanish University Hospital

Background: Biologics for moderate-to-severe psoriasis are expensive and treatment substitutions may vastly increase cost. Moreover, administration regimens in routine practice may differ from recommended guidelines. Objectives: To evaluate long-term effectiveness, regimen, drug-survival, and efficiency of self-administered biologics in clinical practice. Methods: We performed a 5-year retrospective study in 72 patients (44 ± 14 years old) with moderate-to-severe psoriasis at the University Hospital La Plana (Vila-real, Spain), treated with subcutaneous biologics. We determined the effectiveness (PASI 75 or PASI < 5), and drug-survival using Kaplan-Meier estimates, and analyzed reasons for …