PG102 Upregulates IL-37 through p38, ERK, and Smad3 Pathways in HaCaT Keratinocytes
IL-37 is an immunomodulatory cytokine that suppresses inflammation in various cell types and disease models. However, its role in keratinocytes has not been clearly understood, and there has been no report on the agents that can increase the expression of IL-37 in keratinocytes. In this study, we in...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/6085801 |
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| _version_ | 1832547554314682368 |
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| author | Hyun-keun Kim Seonung Lim Min-Jung Bae Wonwoo Lee Sunyoung Kim |
| author_facet | Hyun-keun Kim Seonung Lim Min-Jung Bae Wonwoo Lee Sunyoung Kim |
| author_sort | Hyun-keun Kim |
| collection | DOAJ |
| description | IL-37 is an immunomodulatory cytokine that suppresses inflammation in various cell types and disease models. However, its role in keratinocytes has not been clearly understood, and there has been no report on the agents that can increase the expression of IL-37 in keratinocytes. In this study, we investigated the effects of silencing IL37 in HaCaT keratinocytes and the molecular mechanisms involved in the upregulation of IL-37 by PG102, a water-soluble extract from Actinidia arguta. It was found that knockdown of IL37 resulted in the augmented expression of antimicrobial peptides (AMPs) in response to cytokine stimulation. PG102 increased the expression of IL-37 at both mRNA and protein levels presumably by enhancing the phosphorylation of Smad3, ERK, and p38. Indeed, when cells were treated with specific inhibitors for these signaling molecules, the expression level of IL-37 was reduced. PG102 also promoted colocalization of phospho-Smad3 and IL-37. Our results suggest that IL-37 inhibits the expression of AMPs and that PG102 upregulates IL-37 through p38, ERK, and Smad3 pathways in HaCaT cells. |
| format | Article |
| id | doaj-art-1d155b3ef2b94ece9b45e9035947a425 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1d155b3ef2b94ece9b45e9035947a4252025-02-03T06:44:17ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/60858016085801PG102 Upregulates IL-37 through p38, ERK, and Smad3 Pathways in HaCaT KeratinocytesHyun-keun Kim0Seonung Lim1Min-Jung Bae2Wonwoo Lee3Sunyoung Kim4School of Biological Sciences, Seoul National University, Seoul 151-742, Republic of KoreaSchool of Biological Sciences, Seoul National University, Seoul 151-742, Republic of KoreaViroMed Co. Ltd., Building 203, Seoul National University, Seoul 151-742, Republic of KoreaViroMed Co. Ltd., Building 203, Seoul National University, Seoul 151-742, Republic of KoreaViroMed Co. Ltd., Building 203, Seoul National University, Seoul 151-742, Republic of KoreaIL-37 is an immunomodulatory cytokine that suppresses inflammation in various cell types and disease models. However, its role in keratinocytes has not been clearly understood, and there has been no report on the agents that can increase the expression of IL-37 in keratinocytes. In this study, we investigated the effects of silencing IL37 in HaCaT keratinocytes and the molecular mechanisms involved in the upregulation of IL-37 by PG102, a water-soluble extract from Actinidia arguta. It was found that knockdown of IL37 resulted in the augmented expression of antimicrobial peptides (AMPs) in response to cytokine stimulation. PG102 increased the expression of IL-37 at both mRNA and protein levels presumably by enhancing the phosphorylation of Smad3, ERK, and p38. Indeed, when cells were treated with specific inhibitors for these signaling molecules, the expression level of IL-37 was reduced. PG102 also promoted colocalization of phospho-Smad3 and IL-37. Our results suggest that IL-37 inhibits the expression of AMPs and that PG102 upregulates IL-37 through p38, ERK, and Smad3 pathways in HaCaT cells.http://dx.doi.org/10.1155/2019/6085801 |
| spellingShingle | Hyun-keun Kim Seonung Lim Min-Jung Bae Wonwoo Lee Sunyoung Kim PG102 Upregulates IL-37 through p38, ERK, and Smad3 Pathways in HaCaT Keratinocytes Mediators of Inflammation |
| title | PG102 Upregulates IL-37 through p38, ERK, and Smad3 Pathways in HaCaT Keratinocytes |
| title_full | PG102 Upregulates IL-37 through p38, ERK, and Smad3 Pathways in HaCaT Keratinocytes |
| title_fullStr | PG102 Upregulates IL-37 through p38, ERK, and Smad3 Pathways in HaCaT Keratinocytes |
| title_full_unstemmed | PG102 Upregulates IL-37 through p38, ERK, and Smad3 Pathways in HaCaT Keratinocytes |
| title_short | PG102 Upregulates IL-37 through p38, ERK, and Smad3 Pathways in HaCaT Keratinocytes |
| title_sort | pg102 upregulates il 37 through p38 erk and smad3 pathways in hacat keratinocytes |
| url | http://dx.doi.org/10.1155/2019/6085801 |
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