2349 The role of interleukin-23 in human melanoma
OBJECTIVES/SPECIFIC AIMS: Interleukin-23 (IL-23) promotes differentiation of naïve T-cells into Th17 cells, which drive the pathogenesis of autoinflammatory conditions such as psoriasis. IL-23-neutralizing antibody therapies are now in use for treatment of psoriasis, with promising results. Studies...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Cambridge University Press
2018-06-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866118001358/type/journal_article |
| _version_ | 1811156722459344896 |
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| author | Aditi Jani Sandeep Chaudhary Zorica Janjetovic Mohammad A. Sherwani Nabiha Yusuf Andrzej Slominski Mohammad Athar Craig Elmets |
| author_facet | Aditi Jani Sandeep Chaudhary Zorica Janjetovic Mohammad A. Sherwani Nabiha Yusuf Andrzej Slominski Mohammad Athar Craig Elmets |
| author_sort | Aditi Jani |
| collection | DOAJ |
| description | OBJECTIVES/SPECIFIC AIMS: Interleukin-23 (IL-23) promotes differentiation of naïve T-cells into Th17 cells, which drive the pathogenesis of autoinflammatory conditions such as psoriasis. IL-23-neutralizing antibody therapies are now in use for treatment of psoriasis, with promising results. Studies in mice have shown that IL-23 plays a role in inhibiting the growth, progression, and metastasis of melanomas. Thus, therapeutic neutralization of IL-23 in patients may inadvertently increase their susceptibility to development of melanoma. In this study, we aim to characterize expression of IL-23 receptors (IL-23R) in human melanocytes and melanoma cells and tissue and to study the effect of IL-23 on growth, proliferation, and tumorigenicity of these cells. METHODS/STUDY POPULATION: IL-23R expression was characterized using immunofluorescence staining, Western blot, and flow cytometric analysis. Response of melanoma and melanocytes to recombinant IL-23 treatment will be studied through similar methods in addition to assays of cell proliferation and tumorigenicity. RESULTS/ANTICIPATED RESULTS: Preliminary immunofluorescence staining and flow cytometry results indicate that both human melanoma and primary melanocytes express IL-23 receptors. Western blot analysis showed that melanoma cell line A375 expressed nearly twice the amount of IL-23R versus normal melanocytes (p<0.05). Based on previous studies, we anticipate that addition of recombinant IL-23 to cultures of melanoma will reduce proliferative potential, and we expect similar addition to normal melanocytes will increase DNA repair mechanisms. DISCUSSION/SIGNIFICANCE OF IMPACT: In showing that human melanocytes and melanoma cells express IL-23 receptors, and potentially showing the inhibitory effect of IL-23 in the development of melanocytic neoplasms, our findings imply that using IL-23 neutralizing therapies may increase risk of developing melanoma, especially in patients who are already susceptible. As such, these therapies must be used with great care in these patients. |
| first_indexed | 2024-04-10T04:54:47Z |
| format | Article |
| id | doaj.art-8889fe9399f944b9ac0ba83c078d961a |
| institution | Directory Open Access Journal |
| issn | 2059-8661 |
| language | English |
| last_indexed | 2024-04-10T04:54:47Z |
| publishDate | 2018-06-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj.art-8889fe9399f944b9ac0ba83c078d961a2023-03-09T12:30:17ZengCambridge University PressJournal of Clinical and Translational Science2059-86612018-06-012323210.1017/cts.2018.1352349 The role of interleukin-23 in human melanomaAditi Jani0Sandeep Chaudhary1Zorica Janjetovic2Mohammad A. Sherwani3Nabiha Yusuf4Andrzej Slominski5Mohammad Athar6Craig Elmets7University of Alabama at BirminghamUniversity of Alabama at BirminghamUniversity of Alabama at BirminghamUniversity of Alabama at BirminghamUniversity of Alabama at BirminghamUniversity of Alabama at BirminghamUniversity of Alabama at BirminghamUniversity of Alabama at BirminghamOBJECTIVES/SPECIFIC AIMS: Interleukin-23 (IL-23) promotes differentiation of naïve T-cells into Th17 cells, which drive the pathogenesis of autoinflammatory conditions such as psoriasis. IL-23-neutralizing antibody therapies are now in use for treatment of psoriasis, with promising results. Studies in mice have shown that IL-23 plays a role in inhibiting the growth, progression, and metastasis of melanomas. Thus, therapeutic neutralization of IL-23 in patients may inadvertently increase their susceptibility to development of melanoma. In this study, we aim to characterize expression of IL-23 receptors (IL-23R) in human melanocytes and melanoma cells and tissue and to study the effect of IL-23 on growth, proliferation, and tumorigenicity of these cells. METHODS/STUDY POPULATION: IL-23R expression was characterized using immunofluorescence staining, Western blot, and flow cytometric analysis. Response of melanoma and melanocytes to recombinant IL-23 treatment will be studied through similar methods in addition to assays of cell proliferation and tumorigenicity. RESULTS/ANTICIPATED RESULTS: Preliminary immunofluorescence staining and flow cytometry results indicate that both human melanoma and primary melanocytes express IL-23 receptors. Western blot analysis showed that melanoma cell line A375 expressed nearly twice the amount of IL-23R versus normal melanocytes (p<0.05). Based on previous studies, we anticipate that addition of recombinant IL-23 to cultures of melanoma will reduce proliferative potential, and we expect similar addition to normal melanocytes will increase DNA repair mechanisms. DISCUSSION/SIGNIFICANCE OF IMPACT: In showing that human melanocytes and melanoma cells express IL-23 receptors, and potentially showing the inhibitory effect of IL-23 in the development of melanocytic neoplasms, our findings imply that using IL-23 neutralizing therapies may increase risk of developing melanoma, especially in patients who are already susceptible. As such, these therapies must be used with great care in these patients.https://www.cambridge.org/core/product/identifier/S2059866118001358/type/journal_article |
| spellingShingle | Aditi Jani Sandeep Chaudhary Zorica Janjetovic Mohammad A. Sherwani Nabiha Yusuf Andrzej Slominski Mohammad Athar Craig Elmets 2349 The role of interleukin-23 in human melanoma Journal of Clinical and Translational Science |
| title | 2349 The role of interleukin-23 in human melanoma |
| title_full | 2349 The role of interleukin-23 in human melanoma |
| title_fullStr | 2349 The role of interleukin-23 in human melanoma |
| title_full_unstemmed | 2349 The role of interleukin-23 in human melanoma |
| title_short | 2349 The role of interleukin-23 in human melanoma |
| title_sort | 2349 the role of interleukin 23 in human melanoma |
| url | https://www.cambridge.org/core/product/identifier/S2059866118001358/type/journal_article |
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