Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells
Skullcapflavone II (SFII), a flavonoid derived from <i>Scutellaria baicalensis</i>, has been reported to have anti-inflammatory properties. However, its therapeutic potential for skin inflammatory diseases and its mechanism are unknown. Therefore, this study aimed to investigate the effe...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/12/6428 |
| _version_ | 1797529970304614400 |
|---|---|
| author | Hanon Lee Dong Hun Lee Jang-Hee Oh Jin Ho Chung |
| author_facet | Hanon Lee Dong Hun Lee Jang-Hee Oh Jin Ho Chung |
| author_sort | Hanon Lee |
| collection | DOAJ |
| description | Skullcapflavone II (SFII), a flavonoid derived from <i>Scutellaria baicalensis</i>, has been reported to have anti-inflammatory properties. However, its therapeutic potential for skin inflammatory diseases and its mechanism are unknown. Therefore, this study aimed to investigate the effect of SFII on TNF-α/IFN-γ-induced atopic dermatitis (AD)-associated cytokines, such as thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). Co-stimulation with TNF-α/IFN-γ in HaCaT cells is a well-established model for induction of pro-inflammatory cytokines. We treated cells with SFII prior to TNF-α/IFN-γ-stimulation and confirmed that it significantly inhibited TARC and MDC expression at the mRNA and protein levels. Additionally, SFII also inhibited the expression of cathepsin S (CTSS), which is associated with itching in patients with AD. Using specific inhibitors, we demonstrated that STAT1, NF-κB, and p38 MAPK mediate TNF-α/IFN-γ-induced TARC and MDC, as well as CTSS expression. Finally, we confirmed that SFII significantly suppressed TNF-α/IFN-γ-induced phosphorylation of STAT1, NF-κB, and p38 MAPK. Taken together, our study indicates that SFII inhibits TNF-α/IFN-γ-induced TARC, MDC, and CTSS expression by regulating STAT1, NF-κB, and p38 MAPK signaling pathways. |
| first_indexed | 2024-03-10T10:22:28Z |
| format | Article |
| id | doaj.art-6e100c4574a74b78a5495fa697bcff70 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:22:28Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6e100c4574a74b78a5495fa697bcff702023-11-22T00:17:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012212642810.3390/ijms22126428Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT CellsHanon Lee0Dong Hun Lee1Jang-Hee Oh2Jin Ho Chung3Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, KoreaDepartment of Dermatology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Dermatology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, KoreaSkullcapflavone II (SFII), a flavonoid derived from <i>Scutellaria baicalensis</i>, has been reported to have anti-inflammatory properties. However, its therapeutic potential for skin inflammatory diseases and its mechanism are unknown. Therefore, this study aimed to investigate the effect of SFII on TNF-α/IFN-γ-induced atopic dermatitis (AD)-associated cytokines, such as thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). Co-stimulation with TNF-α/IFN-γ in HaCaT cells is a well-established model for induction of pro-inflammatory cytokines. We treated cells with SFII prior to TNF-α/IFN-γ-stimulation and confirmed that it significantly inhibited TARC and MDC expression at the mRNA and protein levels. Additionally, SFII also inhibited the expression of cathepsin S (CTSS), which is associated with itching in patients with AD. Using specific inhibitors, we demonstrated that STAT1, NF-κB, and p38 MAPK mediate TNF-α/IFN-γ-induced TARC and MDC, as well as CTSS expression. Finally, we confirmed that SFII significantly suppressed TNF-α/IFN-γ-induced phosphorylation of STAT1, NF-κB, and p38 MAPK. Taken together, our study indicates that SFII inhibits TNF-α/IFN-γ-induced TARC, MDC, and CTSS expression by regulating STAT1, NF-κB, and p38 MAPK signaling pathways.https://www.mdpi.com/1422-0067/22/12/6428Skullcapflavone IITARCMDCCTSSSTAT1NF-κB |
| spellingShingle | Hanon Lee Dong Hun Lee Jang-Hee Oh Jin Ho Chung Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells International Journal of Molecular Sciences Skullcapflavone II TARC MDC CTSS STAT1 NF-κB |
| title | Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells |
| title_full | Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells |
| title_fullStr | Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells |
| title_full_unstemmed | Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells |
| title_short | Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells |
| title_sort | skullcapflavone ii suppresses tnf α ifn γ induced tarc mdc and ctss production in hacat cells |
| topic | Skullcapflavone II TARC MDC CTSS STAT1 NF-κB |
| url | https://www.mdpi.com/1422-0067/22/12/6428 |
| work_keys_str_mv | AT hanonlee skullcapflavoneiisuppressestnfaifnginducedtarcmdcandctssproductioninhacatcells AT donghunlee skullcapflavoneiisuppressestnfaifnginducedtarcmdcandctssproductioninhacatcells AT jangheeoh skullcapflavoneiisuppressestnfaifnginducedtarcmdcandctssproductioninhacatcells AT jinhochung skullcapflavoneiisuppressestnfaifnginducedtarcmdcandctssproductioninhacatcells |