resolvin-d1 and Psoriasis

Resolvin D1 (RvD1) is an endogenous lipid mediator that originated from docosahexaenoic acid that stimulates a bimodal mechanism in the anti-inflammatory activity in addition to regulation of the inflammatory reaction. The study aimed at assessing the tissue level of RvD1 in psoriasis to study its role in the etiopathogenesis of psoriasis, studying the action of NB-UVB on the level of resolvin D1 in psoriasis, and raising the possibility of using resolvin D1 as a new therapy for psoriasis in the future. This case-control study included 20 psoriasis patients and 20 healthy controls. Patients took narrowband ultraviolet B (NB-UVB) for 36 sessions. Skin biopsies were taken before and after treatment from patients and from controls to assess the expression of RvD1 by a quantitative real-time polymerase chain reaction. Our findings revealed a statistically significant difference (P < .001) between psoriasis patients (either before or after treatment) and controls with lower levels of RvD1 in psoriasis patients. On comparing the RvD1 levels in psoriasis patients before and after treatment, a statistically significant increase was detected after treatment (P < .001). Tissue RvD1 levels in psoriasis patients were lower than healthy controls and increased after NB-UVB treatment in psoriasis patients. Thus, it is suggested that RvD1 might have a role in the etiopathogenesis of psoriasis. Moreover, the significantly up-regulated tissue levels of RvD1 in patients after treatment with NB-UVB highlighted a novel mechanism of phototherapy-mediated response in psoriasis by up-regulating RvD1 level.

Topics: Case-Control Studies; Docosahexaenoic Acids; Humans; Phototherapy; Psoriasis; Ultraviolet Therapy

Resolvin D1 (RvD1), a pro-resolution lipid mediator derived from docosahexaenoic acid (DHA), has been described to promote several kinds of inflammatory resolution. However, the effects and anti-inflammatory mechanisms of RvD1 on psoriasis have not been previously reported.. The present study aimed to determine the protective effects and the underlying mechanisms of RvD1 on imiquimod (IMQ)-induced psoriasiform dermatitis.. Mice were topically treated with IMQ to develop psoriasiform dermatitis on their shaved back, pretreated intraperitoneally (i.p.) with or without RvD1 or tert-butoxycarbonyl Met-Leu-Phe peptide (Boc), a lipoxin A4 (ALX) receptor antagonist. The severity was monitored and graded using a modified human scoring system, the Psoriasis Area and Severity Index (PASI), histopathology, and the signature cytokines of psoriasis (IL-23, IL-17, IL-22 and TNF-α). The mRNA and protein levels of inflammatory cytokines were quantified by quantitative real-time PCR (QRT-PCR) and ELISA. The expressions of signaling proteins MAPKs and NF-κB p65 were analyzed using western blotting. Electrophoretic mobility shift assay (EMSA) was used to check NF-κB p65 DNA binding activity.. Our study showed that RvD1 alleviated IMQ-induced psoriasiform dermatitis and improved skin pathological changes. RvD1 markedly inhibited IMQ-induced activation of ERK1/2, p38, JNK (c-Jun N-terminal protein kinase, a subfamily of MAPKs), and NF-κB. Furthermore, pretreatment with Boc, would not exacerbate skin inflammation of IMQ-induced mice, but significantly reversed the beneficial effects of RvD1 on IMQ-induced psoriasiform inflammation.. RvD1 can obviously improve skin inflammation in IMQ-induced mice psoriasiform dermatitis. The protective mechanisms might be related to its selective reaction with lipoxin A4 receptor/Formyl-peptide receptor 2 (ALX/FPR2), by downregulating relevant cytokines of the IL-23/IL-17 axis expression, the inhibition of MAPKs and NF-κB signaling transduction pathways. Thus, these results show that RvD1 could be a possible candidate for psoriasis therapy.

Topics: Administration, Cutaneous; Aminoquinolines; Animals; Anti-Inflammatory Agents; Dermatitis; Disease Models, Animal; Docosahexaenoic Acids; Drug Evaluation, Preclinical; Humans; Imiquimod; Male; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; NF-kappa B; Psoriasis; Severity of Illness Index; Signal Transduction; Skin; Skin Cream