PMID- 35280398 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220315 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 10 IP - 4 DP - 2022 Feb TI - Polyinosinic:polycytidylic acid aggravates calcipotriol-induced atopic dermatitis-like skin lesions in mice by increasing the expression of thymic stromal lymphopoietin. PG - 209 LID - 10.21037/atm-22-282 [doi] LID - 209 AB - BACKGROUND: Polyinosinic:polycytidylic acid [poly (I:C)] is a synthetic viral double-stranded RNA analog that can activate Toll-like receptor 3 (TLR3) and induce the release of thymic stromal lymphopoietin (TSLP). TSLP has been shown to contribute to atopic dermatitis (AD). This study explored the effects of poly (I:C) in a calcipotriol-induced model of murine AD. METHODS: Calcipotriol (MC903) was used to establish AD-like mice model. Mice in the MC903 + poly (I:C) group were then treated with poly (I:C) in a concentration of 5 microg/g bodyweight. The impact of poly (I:C) treatment on these animals was assessed based upon changes in lesions, bodyweight, ear thickness, and histopathological findings. In addition, serum interleukin 4 (IL-4), interferon-gamma (IFN-gamma), immunoglobulin E (IgE), IL-13, and TSLP levels were measured using enzyme-linked immunosorbent assay (ELISA), while tissue IL-13 and TSLP levels were assessed using ELISA, Western blotting, and immunohistochemical staining, and mast cell infiltration was assessed through toluidine blue (TBO) staining. RESULTS: Relative to vehicle control treatment, poly (I:C) administration was associated with a significant exacerbation of calcipotriol-induced AD-like murine skin lesions. In animals treated with poly (I:C), the levels of serum IL-4, IL-13 and TSLP increased significantly, while the level of IFN-gamma did not change. It also increased IL-13 and TSLP levels in skin lesions relative to the control-group mice and increased dermal mast cell infiltration and IgE production. CONCLUSIONS: These data indicate that poly (I:C) treatment and exogenous activation of TLR3 exacerbate murine calcipotriol-induced AD-like skin lesions in part by increasing the production of TSLP and other T-helper 2 (Th2)-related cytokines. KEYWORDS: Atopic dermatitis (AD); polyinosinic:polycytidylic acid [poly (I:C)]; thymic stromal lymphopoietin (TSLP); Toll-like receptor 3 (TLR3). CI - 2022 Annals of Translational Medicine. All rights reserved. FAU - Wan, Haoyue AU - Wan H AD - Department of Dermatology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. FAU - Yang, Huixue AU - Yang H AD - Department of Dermatology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. FAU - Wei, Mingjing AU - Wei M AD - Department of Dermatology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. FAU - Chen, Wenqi AU - Chen W AD - Department of Dermatology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC8908153 COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-282/coif). All authors report funding from Nanjing Medical Science and Technology Development Project (Grant No. YKK16134). The authors have no other conflicts of interest to declare. EDAT- 2022/03/15 06:00 MHDA- 2022/03/15 06:01 PMCR- 2022/02/01 CRDT- 2022/03/14 05:10 PHST- 2021/12/22 00:00 [received] PHST- 2022/02/18 00:00 [accepted] PHST- 2022/03/14 05:10 [entrez] PHST- 2022/03/15 06:00 [pubmed] PHST- 2022/03/15 06:01 [medline] PHST- 2022/02/01 00:00 [pmc-release] AID - atm-10-04-209 [pii] AID - 10.21037/atm-22-282 [doi] PST - ppublish SO - Ann Transl Med. 2022 Feb;10(4):209. doi: 10.21037/atm-22-282.