Limits...
Interleukin-1β regulates the expression of glucocorticoid receptor isoforms in nasal polyps in vitro via p38 MAPK and JNK signal transduction pathways.

Wang Z, Li P, Zhang Q, Lv H, Liu J, Si J - J Inflamm (Lond) (2015)

Bottom Line: The expression of GRβ increased more significantly than that of GRα, and the GRα/GRβ ratio decreased in time- and concentration-dependent manners.Statistically significant differences were found in the GRα/GRβ ratio and the mRNA expression of phospho-p38 MAPK and phospho-JNK between the IL-1β-induced groups and the control groups (P < 0.05).None of the specific inhibitors of ERK, PI3K or PKC had any influence on the expression of GR isoforms.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology-Head and Neck Surgery, Xuan Wu Hospital, Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, 100053 PR China.

ABSTRACT

Background: To explore the upstream signal transduction mechanisms responsible for the imbalanced expression of glucocorticoid receptor (GR) isoforms in chronic rhinosinusitis (CRS) mucosa.

Methods: An in vitro model of Glucocorticoid resistance was established by inducing nasal polyp tissue with IL-1β. Changes in the protein and mRNA expression of GRα, GRβ and the key enzymes in the p38 MAPK and JNK signal pathways were measured, respectively, before and after being induced with different doses of IL-1β and specific inhibitors of p38 MAPK, JNK, ERK, PI3K and PKC. The Glucocorticoid sensitivity was measured using in vitro Glucocorticoid binding assay. Analysis of variance (ANOVA) was used to analyze the data.

Results: The mRNA and protein expression levels of GRα, GRβ and key enzymes of the p38 MAPK and JNK pathways increased both in time- and concentration-dependent manners in IL-1β-induced nasal polyp tissue. The expression of GRβ increased more significantly than that of GRα, and the GRα/GRβ ratio decreased in time- and concentration-dependent manners. Statistically significant differences were found in the GRα/GRβ ratio and the mRNA expression of phospho-p38 MAPK and phospho-JNK between the IL-1β-induced groups and the control groups (P < 0.05). Either a specific inhibitor of the p38 MAPK pathway or a specific inhibitor of the JNK pathway increased the GRα/GRβ ratio and the Glucocorticoid affinity. None of the specific inhibitors of ERK, PI3K or PKC had any influence on the expression of GR isoforms.

Conclusion: Our results demonstrated that the imbalanced expression of GR isoforms in nasal polyp tissue induced by IL-1β in vitro is mediated through the p38 MAPK and JNK signal pathways.

No MeSH data available.


Related in: MedlinePlus

The expression of GR isoforms induced by IL-1β with different time length in vitro. A represents Western blot results of IL-1β-induced protein expression of GR isoforms. Lanes 1-4 represent the expression in sample groups treated with IL-1β-treated for 0 h, 10 h, 20 h and 30 h respectively. The GRα and GRβ expression increased with longer IL-1β-inducing time. B represents the densitometry value (Western blot bands in 2A) ratio of GR isoforms and β-actin. The protein expression of GRα and GRβ increased as the IL-1β-inducing time was increased, and the GRβ expression increased more significantly than the GRα expression. C represents the ratio of GR isoforms mRNA between IL-1β-induced groups and the control group (0 h). The mRNA expression of GRα and GRβ increased as the IL-1β-inducing time was increased, and the GRβ expression increased more significantly than the GRα expression. D represents the GRα/GRβ mRNA expression (measured by FQ-RT-PCR) ratio induced by IL-1β. The GRα/GRβ ratio decreased with the increase of IL-1β-inducing time in nasal polyp tissue. The data presented are means ± SD of three independent experiments with similar trend.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4308899&req=5

Fig2: The expression of GR isoforms induced by IL-1β with different time length in vitro. A represents Western blot results of IL-1β-induced protein expression of GR isoforms. Lanes 1-4 represent the expression in sample groups treated with IL-1β-treated for 0 h, 10 h, 20 h and 30 h respectively. The GRα and GRβ expression increased with longer IL-1β-inducing time. B represents the densitometry value (Western blot bands in 2A) ratio of GR isoforms and β-actin. The protein expression of GRα and GRβ increased as the IL-1β-inducing time was increased, and the GRβ expression increased more significantly than the GRα expression. C represents the ratio of GR isoforms mRNA between IL-1β-induced groups and the control group (0 h). The mRNA expression of GRα and GRβ increased as the IL-1β-inducing time was increased, and the GRβ expression increased more significantly than the GRα expression. D represents the GRα/GRβ mRNA expression (measured by FQ-RT-PCR) ratio induced by IL-1β. The GRα/GRβ ratio decreased with the increase of IL-1β-inducing time in nasal polyp tissue. The data presented are means ± SD of three independent experiments with similar trend.

Mentions: Nasal polyp tissues were cultured in the presence of 20 ng/mL IL-1β for 0 h, 10 h, 20 h and 30 h respectively. IL-1β induced the expression of GRα and GRβ in a time-dependent manner, and the expression of GRβ increased more significantly than that of GRα (Figure 2A,B and C). IL-1β treatment led to lower GRα/GRβ ratio in a time-dependent manner (Figure 2D). The GRα/GRβ ratio at the mRNA and protein levels observed in each treatment group was significantly lower than that of the control group (X2 = 52.321, P = 0.002; X2 = 38.742, P = 0.001).Figure 2


Interleukin-1β regulates the expression of glucocorticoid receptor isoforms in nasal polyps in vitro via p38 MAPK and JNK signal transduction pathways.

Wang Z, Li P, Zhang Q, Lv H, Liu J, Si J - J Inflamm (Lond) (2015)

The expression of GR isoforms induced by IL-1β with different time length in vitro. A represents Western blot results of IL-1β-induced protein expression of GR isoforms. Lanes 1-4 represent the expression in sample groups treated with IL-1β-treated for 0 h, 10 h, 20 h and 30 h respectively. The GRα and GRβ expression increased with longer IL-1β-inducing time. B represents the densitometry value (Western blot bands in 2A) ratio of GR isoforms and β-actin. The protein expression of GRα and GRβ increased as the IL-1β-inducing time was increased, and the GRβ expression increased more significantly than the GRα expression. C represents the ratio of GR isoforms mRNA between IL-1β-induced groups and the control group (0 h). The mRNA expression of GRα and GRβ increased as the IL-1β-inducing time was increased, and the GRβ expression increased more significantly than the GRα expression. D represents the GRα/GRβ mRNA expression (measured by FQ-RT-PCR) ratio induced by IL-1β. The GRα/GRβ ratio decreased with the increase of IL-1β-inducing time in nasal polyp tissue. The data presented are means ± SD of three independent experiments with similar trend.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4308899&req=5

Fig2: The expression of GR isoforms induced by IL-1β with different time length in vitro. A represents Western blot results of IL-1β-induced protein expression of GR isoforms. Lanes 1-4 represent the expression in sample groups treated with IL-1β-treated for 0 h, 10 h, 20 h and 30 h respectively. The GRα and GRβ expression increased with longer IL-1β-inducing time. B represents the densitometry value (Western blot bands in 2A) ratio of GR isoforms and β-actin. The protein expression of GRα and GRβ increased as the IL-1β-inducing time was increased, and the GRβ expression increased more significantly than the GRα expression. C represents the ratio of GR isoforms mRNA between IL-1β-induced groups and the control group (0 h). The mRNA expression of GRα and GRβ increased as the IL-1β-inducing time was increased, and the GRβ expression increased more significantly than the GRα expression. D represents the GRα/GRβ mRNA expression (measured by FQ-RT-PCR) ratio induced by IL-1β. The GRα/GRβ ratio decreased with the increase of IL-1β-inducing time in nasal polyp tissue. The data presented are means ± SD of three independent experiments with similar trend.
Mentions: Nasal polyp tissues were cultured in the presence of 20 ng/mL IL-1β for 0 h, 10 h, 20 h and 30 h respectively. IL-1β induced the expression of GRα and GRβ in a time-dependent manner, and the expression of GRβ increased more significantly than that of GRα (Figure 2A,B and C). IL-1β treatment led to lower GRα/GRβ ratio in a time-dependent manner (Figure 2D). The GRα/GRβ ratio at the mRNA and protein levels observed in each treatment group was significantly lower than that of the control group (X2 = 52.321, P = 0.002; X2 = 38.742, P = 0.001).Figure 2

Bottom Line: The expression of GRβ increased more significantly than that of GRα, and the GRα/GRβ ratio decreased in time- and concentration-dependent manners.Statistically significant differences were found in the GRα/GRβ ratio and the mRNA expression of phospho-p38 MAPK and phospho-JNK between the IL-1β-induced groups and the control groups (P < 0.05).None of the specific inhibitors of ERK, PI3K or PKC had any influence on the expression of GR isoforms.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology-Head and Neck Surgery, Xuan Wu Hospital, Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, 100053 PR China.

ABSTRACT

Background: To explore the upstream signal transduction mechanisms responsible for the imbalanced expression of glucocorticoid receptor (GR) isoforms in chronic rhinosinusitis (CRS) mucosa.

Methods: An in vitro model of Glucocorticoid resistance was established by inducing nasal polyp tissue with IL-1β. Changes in the protein and mRNA expression of GRα, GRβ and the key enzymes in the p38 MAPK and JNK signal pathways were measured, respectively, before and after being induced with different doses of IL-1β and specific inhibitors of p38 MAPK, JNK, ERK, PI3K and PKC. The Glucocorticoid sensitivity was measured using in vitro Glucocorticoid binding assay. Analysis of variance (ANOVA) was used to analyze the data.

Results: The mRNA and protein expression levels of GRα, GRβ and key enzymes of the p38 MAPK and JNK pathways increased both in time- and concentration-dependent manners in IL-1β-induced nasal polyp tissue. The expression of GRβ increased more significantly than that of GRα, and the GRα/GRβ ratio decreased in time- and concentration-dependent manners. Statistically significant differences were found in the GRα/GRβ ratio and the mRNA expression of phospho-p38 MAPK and phospho-JNK between the IL-1β-induced groups and the control groups (P < 0.05). Either a specific inhibitor of the p38 MAPK pathway or a specific inhibitor of the JNK pathway increased the GRα/GRβ ratio and the Glucocorticoid affinity. None of the specific inhibitors of ERK, PI3K or PKC had any influence on the expression of GR isoforms.

Conclusion: Our results demonstrated that the imbalanced expression of GR isoforms in nasal polyp tissue induced by IL-1β in vitro is mediated through the p38 MAPK and JNK signal pathways.

No MeSH data available.


Related in: MedlinePlus