Roles of keratinocyte inflammation in oral cancer

Regulating the prostaglandin E2, interleukin-6 and TNF-α production of oral epithelial cells by areca nut extract and arecoline

Jiiang Huei Jeng, Ying Jan Wang, Bor Luen Chiang, Po Hsuen Lee, Chiu Po Chan, Yuan Soon Ho, Tong Mei Wang, Jang Jaer Lee, Liang Jiunn Hahn, Mei Chi Chang

Research output: Contribution to journalArticle

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Abstract

Betel quid (BQ) chewing is an etiologic factor of oral cancer and submucus fibrosis (OSF). Keratinocyte inflammation is crucial for the pathogenesis of cancer and tissue fibrosis. We found that areca nut (AN) extract (100-400 μg/ml) induced PGE2 production by KB cells by 2.34- to 23.1-fold and also TNF-α production by gingival keratinocytes (GK). Arecoline (0.2-1.2 mM) elevated PGE2 production by KB cells by 2.5- to 6.1-fold. AN extract (200-400 μg/ml also induced IL-6 production by GK (7.5- to 8.4-fold) and KB cells. In contrast, arecoline (0.1-1.2 mM) suppressed IL-6 production by GK and KB cells, with 42-81 and 41-63% inhibition, respectively. A 48 h exposure of GK to 800-1200 μg/ml AN extract led to 37-69% cell death. Arecoline cytotoxicity to GK was noted at concentrations of 0.8-1.2 mM, which led to 28-38% cell death. AN extract (400-800 μg/ml) induced Cox-2 and IL-6 mRNA expression and also COX-2 protein production by KB cells. IL-6 (5-100 ng/ml) suppressed GK growth by 20-33%, but enhanced oral fibroblast (OMF) and KB cell growth. PGE2 (0.05-5 μg/ml) and anti-IL-6 antibody (ab) (50-1000 ng/ml) showed little effect on GK and KB cell growth. Incubation of GK and KB cells with aspirin, antiIL-6 ab and anti-TNF-α ab showed little effect on arecoline- and AN-induced cytotoxicity, cell cycle arrest and apoptosis. Exposure to anti-TNF-α ab slightly affected arecoline- and AN-modulated PGE2 and IL-6 production by GK and KB cells. Arecoline- and AN-conditioned medium decreased phytohemagglutinin-mediated CD4+ and CD8+ T cell activation. These results indicate that BQ chewing contributes to the pathogenesis of cancer and OSF by impairing T cell activation and by induction of PGE2, TNF-α and IL-6 production, which affect oral mucosal inflammation and growth of OMF and oral epithelial cells.

Original languageEnglish
Pages (from-to)1301-1315
Number of pages15
JournalCarcinogenesis
Volume24
Issue number8
DOIs
Publication statusPublished - Aug 1 2003

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Arecoline
Areca
Nuts
KB Cells
Mouth Neoplasms
Keratinocytes
Dinoprostone
Interleukin-6
Epithelial Cells
Inflammation
Fibrosis
Mastication
Growth
Anti-Idiotypic Antibodies
Cell Death
T-Lymphocytes
Antibodies
Interleukin-5
Phytohemagglutinins
Conditioned Culture Medium

ASJC Scopus subject areas

  • Cancer Research

Cite this

Roles of keratinocyte inflammation in oral cancer : Regulating the prostaglandin E2, interleukin-6 and TNF-α production of oral epithelial cells by areca nut extract and arecoline. / Jeng, Jiiang Huei; Wang, Ying Jan; Chiang, Bor Luen; Lee, Po Hsuen; Chan, Chiu Po; Ho, Yuan Soon; Wang, Tong Mei; Lee, Jang Jaer; Hahn, Liang Jiunn; Chang, Mei Chi.

In: Carcinogenesis, Vol. 24, No. 8, 01.08.2003, p. 1301-1315.

Research output: Contribution to journalArticle

Jeng, Jiiang Huei ; Wang, Ying Jan ; Chiang, Bor Luen ; Lee, Po Hsuen ; Chan, Chiu Po ; Ho, Yuan Soon ; Wang, Tong Mei ; Lee, Jang Jaer ; Hahn, Liang Jiunn ; Chang, Mei Chi. / Roles of keratinocyte inflammation in oral cancer : Regulating the prostaglandin E2, interleukin-6 and TNF-α production of oral epithelial cells by areca nut extract and arecoline. In: Carcinogenesis. 2003 ; Vol. 24, No. 8. pp. 1301-1315.
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abstract = "Betel quid (BQ) chewing is an etiologic factor of oral cancer and submucus fibrosis (OSF). Keratinocyte inflammation is crucial for the pathogenesis of cancer and tissue fibrosis. We found that areca nut (AN) extract (100-400 μg/ml) induced PGE2 production by KB cells by 2.34- to 23.1-fold and also TNF-α production by gingival keratinocytes (GK). Arecoline (0.2-1.2 mM) elevated PGE2 production by KB cells by 2.5- to 6.1-fold. AN extract (200-400 μg/ml also induced IL-6 production by GK (7.5- to 8.4-fold) and KB cells. In contrast, arecoline (0.1-1.2 mM) suppressed IL-6 production by GK and KB cells, with 42-81 and 41-63{\%} inhibition, respectively. A 48 h exposure of GK to 800-1200 μg/ml AN extract led to 37-69{\%} cell death. Arecoline cytotoxicity to GK was noted at concentrations of 0.8-1.2 mM, which led to 28-38{\%} cell death. AN extract (400-800 μg/ml) induced Cox-2 and IL-6 mRNA expression and also COX-2 protein production by KB cells. IL-6 (5-100 ng/ml) suppressed GK growth by 20-33{\%}, but enhanced oral fibroblast (OMF) and KB cell growth. PGE2 (0.05-5 μg/ml) and anti-IL-6 antibody (ab) (50-1000 ng/ml) showed little effect on GK and KB cell growth. Incubation of GK and KB cells with aspirin, antiIL-6 ab and anti-TNF-α ab showed little effect on arecoline- and AN-induced cytotoxicity, cell cycle arrest and apoptosis. Exposure to anti-TNF-α ab slightly affected arecoline- and AN-modulated PGE2 and IL-6 production by GK and KB cells. Arecoline- and AN-conditioned medium decreased phytohemagglutinin-mediated CD4+ and CD8+ T cell activation. These results indicate that BQ chewing contributes to the pathogenesis of cancer and OSF by impairing T cell activation and by induction of PGE2, TNF-α and IL-6 production, which affect oral mucosal inflammation and growth of OMF and oral epithelial cells.",
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T1 - Roles of keratinocyte inflammation in oral cancer

T2 - Regulating the prostaglandin E2, interleukin-6 and TNF-α production of oral epithelial cells by areca nut extract and arecoline

AU - Jeng, Jiiang Huei

AU - Wang, Ying Jan

AU - Chiang, Bor Luen

AU - Lee, Po Hsuen

AU - Chan, Chiu Po

AU - Ho, Yuan Soon

AU - Wang, Tong Mei

AU - Lee, Jang Jaer

AU - Hahn, Liang Jiunn

AU - Chang, Mei Chi

PY - 2003/8/1

Y1 - 2003/8/1

N2 - Betel quid (BQ) chewing is an etiologic factor of oral cancer and submucus fibrosis (OSF). Keratinocyte inflammation is crucial for the pathogenesis of cancer and tissue fibrosis. We found that areca nut (AN) extract (100-400 μg/ml) induced PGE2 production by KB cells by 2.34- to 23.1-fold and also TNF-α production by gingival keratinocytes (GK). Arecoline (0.2-1.2 mM) elevated PGE2 production by KB cells by 2.5- to 6.1-fold. AN extract (200-400 μg/ml also induced IL-6 production by GK (7.5- to 8.4-fold) and KB cells. In contrast, arecoline (0.1-1.2 mM) suppressed IL-6 production by GK and KB cells, with 42-81 and 41-63% inhibition, respectively. A 48 h exposure of GK to 800-1200 μg/ml AN extract led to 37-69% cell death. Arecoline cytotoxicity to GK was noted at concentrations of 0.8-1.2 mM, which led to 28-38% cell death. AN extract (400-800 μg/ml) induced Cox-2 and IL-6 mRNA expression and also COX-2 protein production by KB cells. IL-6 (5-100 ng/ml) suppressed GK growth by 20-33%, but enhanced oral fibroblast (OMF) and KB cell growth. PGE2 (0.05-5 μg/ml) and anti-IL-6 antibody (ab) (50-1000 ng/ml) showed little effect on GK and KB cell growth. Incubation of GK and KB cells with aspirin, antiIL-6 ab and anti-TNF-α ab showed little effect on arecoline- and AN-induced cytotoxicity, cell cycle arrest and apoptosis. Exposure to anti-TNF-α ab slightly affected arecoline- and AN-modulated PGE2 and IL-6 production by GK and KB cells. Arecoline- and AN-conditioned medium decreased phytohemagglutinin-mediated CD4+ and CD8+ T cell activation. These results indicate that BQ chewing contributes to the pathogenesis of cancer and OSF by impairing T cell activation and by induction of PGE2, TNF-α and IL-6 production, which affect oral mucosal inflammation and growth of OMF and oral epithelial cells.

AB - Betel quid (BQ) chewing is an etiologic factor of oral cancer and submucus fibrosis (OSF). Keratinocyte inflammation is crucial for the pathogenesis of cancer and tissue fibrosis. We found that areca nut (AN) extract (100-400 μg/ml) induced PGE2 production by KB cells by 2.34- to 23.1-fold and also TNF-α production by gingival keratinocytes (GK). Arecoline (0.2-1.2 mM) elevated PGE2 production by KB cells by 2.5- to 6.1-fold. AN extract (200-400 μg/ml also induced IL-6 production by GK (7.5- to 8.4-fold) and KB cells. In contrast, arecoline (0.1-1.2 mM) suppressed IL-6 production by GK and KB cells, with 42-81 and 41-63% inhibition, respectively. A 48 h exposure of GK to 800-1200 μg/ml AN extract led to 37-69% cell death. Arecoline cytotoxicity to GK was noted at concentrations of 0.8-1.2 mM, which led to 28-38% cell death. AN extract (400-800 μg/ml) induced Cox-2 and IL-6 mRNA expression and also COX-2 protein production by KB cells. IL-6 (5-100 ng/ml) suppressed GK growth by 20-33%, but enhanced oral fibroblast (OMF) and KB cell growth. PGE2 (0.05-5 μg/ml) and anti-IL-6 antibody (ab) (50-1000 ng/ml) showed little effect on GK and KB cell growth. Incubation of GK and KB cells with aspirin, antiIL-6 ab and anti-TNF-α ab showed little effect on arecoline- and AN-induced cytotoxicity, cell cycle arrest and apoptosis. Exposure to anti-TNF-α ab slightly affected arecoline- and AN-modulated PGE2 and IL-6 production by GK and KB cells. Arecoline- and AN-conditioned medium decreased phytohemagglutinin-mediated CD4+ and CD8+ T cell activation. These results indicate that BQ chewing contributes to the pathogenesis of cancer and OSF by impairing T cell activation and by induction of PGE2, TNF-α and IL-6 production, which affect oral mucosal inflammation and growth of OMF and oral epithelial cells.

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