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STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma

Interleukin (IL)-22 is a member of the IL-10 family. Its main targets are epithelial cells, not immune cells. We examined IL-22 signal transduction in oral squamous cell carcinoma (OSCC) cells. Immunohistochemical staining revealed that IL-22R was expressed more highly in OSCC compared to normal reg...

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Autores principales: NAHER, LUTFUN, KIYOSHIMA, TAMOTSU, KOBAYASHI, IEYOSHI, WADA, HIROKO, NAGATA, KENGO, FUJIWARA, HIROAKI, OOKUMA, YUKIKO F., OZEKI, SATORU, NAKAMURA, SEIJI, SAKAI, HIDETAKA
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583669/
https://www.ncbi.nlm.nih.gov/pubmed/22922995
http://dx.doi.org/10.3892/ijo.2012.1594
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author NAHER, LUTFUN
KIYOSHIMA, TAMOTSU
KOBAYASHI, IEYOSHI
WADA, HIROKO
NAGATA, KENGO
FUJIWARA, HIROAKI
OOKUMA, YUKIKO F.
OZEKI, SATORU
NAKAMURA, SEIJI
SAKAI, HIDETAKA
author_facet NAHER, LUTFUN
KIYOSHIMA, TAMOTSU
KOBAYASHI, IEYOSHI
WADA, HIROKO
NAGATA, KENGO
FUJIWARA, HIROAKI
OOKUMA, YUKIKO F.
OZEKI, SATORU
NAKAMURA, SEIJI
SAKAI, HIDETAKA
author_sort NAHER, LUTFUN
collection PubMed
description Interleukin (IL)-22 is a member of the IL-10 family. Its main targets are epithelial cells, not immune cells. We examined IL-22 signal transduction in oral squamous cell carcinoma (OSCC) cells. Immunohistochemical staining revealed that IL-22R was expressed more highly in OSCC compared to normal regions. An IL-22R signal was also observed in metastatic OSCC cells in the lymph node. RT-PCR showed that the human OSCC cell lines MISK81-5, HSC-3, HSC-4, SAS and SQUU-B expressed IL-22 receptor chains. Immunoblotting showed that IL-22 induced a transient tyrosine phosphorylation of STAT3 (pY705-STAT3) in MISK81-5 cells. The change in the serine phosphorylation of STAT3 was subtle during the examination periods. Simultaneously, pY705-STAT3 activation in HSC-3 cells was undetectable after IL-22 stimulation. Immunocytochemistry demonstrated that IL-22 induced the translocation of phosphorylated STAT3 into the nucleus of MISK81-5 cells. IL-22 temporarily upregulated the expression of anti-apoptotic and mitogenic genes such as Bcl-x, survivin and c-Myc, as well as SOCS3. IL-22 transiently activated ERK1/2 and induced a delayed phosphorylation of p38 MAP kinase, but negligibly involved the activation of NF-κB in MISK81-5 cells. MISK81-5 and SQUU-B cells treated with IL-22 showed mild cellular proliferation. MISK81-5, HSC-4 and SAS cells treated with IL-22 downregulated the keratinocyte differentiation-related genes compared with unstimulated cells. Conversely, STAT3 suppression by STAT3 siRNA strongly disrupted the down-regulation of these genes by IL-22, but it did not significantly affect the activation of ERK1/2 by IL-22. The OSCC cells used in this study upregulated the expression of SERPINB3/4 (SCCA1/2), well-known SCC markers, following treatment with IL-22. These results indicate that IL-22 differentially activates the STAT3 signaling system depending on the type of OSCC. IL-22 may therefore play a role in tumor growth, cell differentiation and progression through STAT3-dependent and -independent pathways.
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spelling pubmed-35836692013-03-04 STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma NAHER, LUTFUN KIYOSHIMA, TAMOTSU KOBAYASHI, IEYOSHI WADA, HIROKO NAGATA, KENGO FUJIWARA, HIROAKI OOKUMA, YUKIKO F. OZEKI, SATORU NAKAMURA, SEIJI SAKAI, HIDETAKA Int J Oncol Articles Interleukin (IL)-22 is a member of the IL-10 family. Its main targets are epithelial cells, not immune cells. We examined IL-22 signal transduction in oral squamous cell carcinoma (OSCC) cells. Immunohistochemical staining revealed that IL-22R was expressed more highly in OSCC compared to normal regions. An IL-22R signal was also observed in metastatic OSCC cells in the lymph node. RT-PCR showed that the human OSCC cell lines MISK81-5, HSC-3, HSC-4, SAS and SQUU-B expressed IL-22 receptor chains. Immunoblotting showed that IL-22 induced a transient tyrosine phosphorylation of STAT3 (pY705-STAT3) in MISK81-5 cells. The change in the serine phosphorylation of STAT3 was subtle during the examination periods. Simultaneously, pY705-STAT3 activation in HSC-3 cells was undetectable after IL-22 stimulation. Immunocytochemistry demonstrated that IL-22 induced the translocation of phosphorylated STAT3 into the nucleus of MISK81-5 cells. IL-22 temporarily upregulated the expression of anti-apoptotic and mitogenic genes such as Bcl-x, survivin and c-Myc, as well as SOCS3. IL-22 transiently activated ERK1/2 and induced a delayed phosphorylation of p38 MAP kinase, but negligibly involved the activation of NF-κB in MISK81-5 cells. MISK81-5 and SQUU-B cells treated with IL-22 showed mild cellular proliferation. MISK81-5, HSC-4 and SAS cells treated with IL-22 downregulated the keratinocyte differentiation-related genes compared with unstimulated cells. Conversely, STAT3 suppression by STAT3 siRNA strongly disrupted the down-regulation of these genes by IL-22, but it did not significantly affect the activation of ERK1/2 by IL-22. The OSCC cells used in this study upregulated the expression of SERPINB3/4 (SCCA1/2), well-known SCC markers, following treatment with IL-22. These results indicate that IL-22 differentially activates the STAT3 signaling system depending on the type of OSCC. IL-22 may therefore play a role in tumor growth, cell differentiation and progression through STAT3-dependent and -independent pathways. D.A. Spandidos 2012-08-21 /pmc/articles/PMC3583669/ /pubmed/22922995 http://dx.doi.org/10.3892/ijo.2012.1594 Text en Copyright © 2012, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
NAHER, LUTFUN
KIYOSHIMA, TAMOTSU
KOBAYASHI, IEYOSHI
WADA, HIROKO
NAGATA, KENGO
FUJIWARA, HIROAKI
OOKUMA, YUKIKO F.
OZEKI, SATORU
NAKAMURA, SEIJI
SAKAI, HIDETAKA
STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma
title STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma
title_full STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma
title_fullStr STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma
title_full_unstemmed STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma
title_short STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma
title_sort stat3 signal transduction through interleukin-22 in oral squamous cell carcinoma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583669/
https://www.ncbi.nlm.nih.gov/pubmed/22922995
http://dx.doi.org/10.3892/ijo.2012.1594
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