Losartan ointment attenuates imiquimod-induced psoriasis-like inflammation.
Administration, Cutaneous
Angiotensin II Type 1 Receptor Blockers
/ administration & dosage
Animals
Anti-Inflammatory Agents
/ administration & dosage
Disease Models, Animal
Imiquimod
Interleukin-17
/ metabolism
Losartan
/ administration & dosage
Male
Mice
Ointments
Psoriasis
/ chemically induced
Receptor, Angiotensin, Type 1
/ metabolism
Skin
/ drug effects
Th17 Cells
/ drug effects
Angiotensin 1 receptor (AT1R)
Imiquimod (IMQ)
Inflammation
Interleukin-17 (IL-17)
Losartan
Mice
Psoriasis
Journal
International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
received:
19
06
2021
revised:
11
09
2021
accepted:
13
09
2021
pubmed:
29
9
2021
medline:
8
2
2022
entrez:
28
9
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
METHODS
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 34583123
pii: S1567-5769(21)00796-7
doi: 10.1016/j.intimp.2021.108160
pii:
doi:
Substances chimiques
Angiotensin II Type 1 Receptor Blockers
0
Anti-Inflammatory Agents
0
Il17a protein, mouse
0
Interleukin-17
0
Ointments
0
Receptor, Angiotensin, Type 1
0
Losartan
JMS50MPO89
Imiquimod
P1QW714R7M
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
108160Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.