Psoriatic inflammation enhances allergic airway inflammation through IL-23/STAT3 signaling in a murine model

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• 作者：Ahmed Nadeem^a ; ^{anadeem@ksu.edu.sa} ; Naif O. Al-Harbi^a ; Mushtaq A. Ansari^a ; Mohammed M. Al-Harbi^a ; Ahmed M. El-Sherbeeny^b ; Khairy M.A. Zoheir^a ; Sabry M. Attia^a ; Mohamed M. Hafez^a ; Othman A. Al-Shabanah^a ; Sheikh F. Ahmad^a
• 关键词：Psoriasis ; Asthma ; IL-23 ; STAT3 ; Th17
• 刊名：Biochemical Pharmacology
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：124
• 期：Complete
• 页码：69-82
• 全文大小：3371 K
• 卷排序：124

文摘

Psoriasis is an autoimmune inflammatory skin disease characterized by activated IL-23/STAT3/Th17 axis. Recently psoriatic inflammation has been shown to be associated with asthma. However, no study has previously explored how psoriatic inflammation affects airway inflammation. Therefore, this study investigated the effect of imiquimod (IMQ)-induced psoriatic inflammation on cockroach extract (CE)-induced airway inflammation in murine models. Mice were subjected to topical and intranasal administration of IMQ and CE to develop psoriatic and airway inflammation respectively. Various analyses in lung/spleen related to inflammation, Th17/Th2/Th1 cell immune responses, and their signature cytokines/transcription factors were carried out. Psoriatic inflammation in allergic mice was associated with increased airway inflammation with concurrent increase in Th2/Th17 cells/signature cytokines/transcription factors. Splenic CD4+ T and CD11c+ dendritic cells in psoriatic mice had increased STAT3/RORC and IL-23 mRNA expression respectively. This led us to explore the effect of systemic IL-23/STAT3 signaling on airway inflammation. Topical application of STA-21, a small molecule STAT3 inhibitor significantly reduced airway inflammation in allergic mice having psoriatic inflammation. On the other hand, adoptive transfer of IL-23-treated splenic CD4+ T cells from allergic mice into naive recipient mice produced mixed neutrophilic/eosinophilic airway inflammation similar to allergic mice with psoriatic inflammation. Our data suggest that systemic IL-23/STAT3 axis is responsible for enhanced airway inflammation during psoriasis. The current study also suggests that only anti-asthma therapy may not be sufficient to alleviate airway inflammatory burden in asthmatics with psoriasis.