Losartan ointment attenuates imiquimod-induced psoriasis-like inflammation

Abstract

Background: Psoriasis is a chronic skin condition associated with interleukin-23/interleukin-17 (IL-23/IL-17) pathway. Recent evidence declares that angiotensin II (Ang II) induces a potent IL-17-related inflammation. Meanwhile, Losartan, an angiotensin one receptor (AT1R) antagonist, attenuates the TH17-related responses. Therefore, we investigated the possible beneficial effects of topically applied Losartan1% ointment on imiquimod (IMQ)-induced psoriasis in mice.

Method: Psoriasis was induced in mice consecutively for five days by topical IMQ on the shaved back. The IMQ-induced psoriasis was treated via topical administration of Losartan1% twice a day. The severity of skin inflammation was evaluated employing Psoriasis Area and Severity Index (PASI) scores. Subsequently, the skin samples were assessed using Baker's scoring system, stereological studies, and biochemical assessment with real-time PCR and immunohistochemistry.

Results: IMQ administration induced plaque-type psoriasis and skin inflammation. We characterized psoriatic lesions by hyperkeratosis, Munro abscess, rete ridges, and marked T-cell infiltrates. IMQ significantly increased epidermal volume, mRNA expression of IL-17a, IL-23, Ang II, AT1R, and TNF-α levels compared with the Placebo group. Topical administration of Losartan1% on IMQ-induced psoriasis significantly reduced the PASI scores and alleviated the erythema and scaling. The treatment significantly decreased the psoriatic thickness and dermal T-cell infiltration. Regarding biochemical assessment, Losartan1% considerably reduced the IMQ-induced increase of IL-17a, Ang II, and AT1R expression in the skin.

Conclusion: Topical Losartan1% significantly alleviates psoriasis by reducing AT1R and IL-17a expression. Our results introduce AT1Rs as a promising therapeutic target in psoriasis and represent a link between angiotensin and TH17-related inflammation. However, the effects of AngII-AT1R systems on IL-17 signaling need to be confirmed by further investigations.

Keywords: Angiotensin 1 receptor (AT1R); Imiquimod (IMQ); Inflammation; Interleukin-17 (IL-17); Losartan; Mice; Psoriasis.