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Overexpression and selectively regulatory roles of IL-23/IL-17 axis in the lesions of oral lichen planus.

Lu R, Zeng X, Han Q, Lin M, Long L, Dan H, Zhou G, Chen Q - Mediators Inflamm. (2014)

Bottom Line: In addition, the expressions of IL-23 and IL-17 are positively correlated in reticular OLP tissues.Results from in vitro studies revealed that exogenous IL-23 could increase the percentage of Th17 cells and IL-17 production in the CD4+T cells from reticular OLP patients.Furthermore, we also found that exogenous IL-17 could significantly enhance the mRNA expressions of β-defensin-2, -3, CCL-20, IL-8, and TNF-α, but not β-defensin-1, CXCL-9, -10, -11, CCL-5, and IL-6 in human oral keratinocytes.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu 610041, China ; The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, No. 237 Luoyu Road, Wuhan 430079, China.

ABSTRACT
Interleukin- (IL-) 23/IL-17 axis is a newly discovered proinflammatory signaling pathway and has been implicated in the pathogenesis of many chronic inflammatory and immune disorders. Here we investigated whether the IL-23/IL-17 axis was present and functional in the lesions of oral lichen planus (OLP), a chronic inflammatory disease affecting the oral mucosa. Using immunohistochemistry and quantitative PCR, we found that the subunits of IL-23 and IL-17 were overexpressed in OLP lesions than in normal oral mucosa tissues. In addition, the expressions of IL-23 and IL-17 are positively correlated in reticular OLP tissues. Results from in vitro studies revealed that exogenous IL-23 could increase the percentage of Th17 cells and IL-17 production in the CD4+T cells from reticular OLP patients. Furthermore, we also found that exogenous IL-17 could significantly enhance the mRNA expressions of β-defensin-2, -3, CCL-20, IL-8, and TNF-α, but not β-defensin-1, CXCL-9, -10, -11, CCL-5, and IL-6 in human oral keratinocytes. Taken together, our results revealed an overexpression pattern and selectively regulatory roles of IL-23/IL-17 axis in the OLP lesions, suggesting that it may be a pivotal regulatory pathway in the complex immune network of OLP lesions.

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Related in: MedlinePlus

Expressions of IL-23 and IL-17 in OLP lesions. (a) The average staining scores of IL-23p19 in erosive OLP lesions (n = 13), reticular OLP lesions (n = 14), and normal oral mucosa tissues (n = 10). (b) The average number of IL-17+ cells per hpf in erosive OLP lesions (n = 13), reticular OLP lesions (n = 14), and normal oral mucosa tissues (n = 10). ((c) and (d)) The mRNA expressions of IL-23p19, IL-12p40, and IL-17 in reticular OLP lesions (n = 14) and normal oral mucosa tissues (n = 10). All data were shown as mean ± SEM.  **P < 0.01;  **P < 0.05; NS: nonsignificantly.
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fig2: Expressions of IL-23 and IL-17 in OLP lesions. (a) The average staining scores of IL-23p19 in erosive OLP lesions (n = 13), reticular OLP lesions (n = 14), and normal oral mucosa tissues (n = 10). (b) The average number of IL-17+ cells per hpf in erosive OLP lesions (n = 13), reticular OLP lesions (n = 14), and normal oral mucosa tissues (n = 10). ((c) and (d)) The mRNA expressions of IL-23p19, IL-12p40, and IL-17 in reticular OLP lesions (n = 14) and normal oral mucosa tissues (n = 10). All data were shown as mean ± SEM.  **P < 0.01;  **P < 0.05; NS: nonsignificantly.

Mentions: To identify whether IL-23/IL-17 is involved in the local pathogenesis of OLP, we firstly detected the expression and distribution of IL-23 p19, a unique subunit of IL-23, and IL-17 in OLP lesions and NOM tissues. Using IHC detection, we observed diffuse and strong expressions of IL-23p19 in both erosive and reticular OLP lesions. The positive staining of IL-23p19 predominantly concentrated on the epithelium of OLP lesions and also on the extracellular matrix of the lamina propria (Figures 1(a)–1(d)). In contrast, only a few keratinocytes in the epidermis layer of the NOM tissues showed weak stain of IL-23p19 (Figures 1(e) and 1(f)). Moreover, we found abundant IL-17 positive stainings on the cytoplasm of the infiltrated lymphocytes in the lesions of both erosive and reticular OLP, but only a few sporadic IL-17+ cells in the normal oral mucosa (Figures 1(g)–1(l)). The statistical data showed that both the erosive and reticular OLP lesions had significantly increased immunostaining scores of IL-23p19, as well as the numbers of IL-17+ cells, compared to the normal oral mucosa. In addition, erosive OLP lesions contained a significantly increased number of IL-17+ cells compared to the reticular OLP lesions. However, there is no significant difference in IL-23p19 staining score between erosive and the reticular OLP lesions (Figures 2(a) and 2(b)).


Overexpression and selectively regulatory roles of IL-23/IL-17 axis in the lesions of oral lichen planus.

Lu R, Zeng X, Han Q, Lin M, Long L, Dan H, Zhou G, Chen Q - Mediators Inflamm. (2014)

Expressions of IL-23 and IL-17 in OLP lesions. (a) The average staining scores of IL-23p19 in erosive OLP lesions (n = 13), reticular OLP lesions (n = 14), and normal oral mucosa tissues (n = 10). (b) The average number of IL-17+ cells per hpf in erosive OLP lesions (n = 13), reticular OLP lesions (n = 14), and normal oral mucosa tissues (n = 10). ((c) and (d)) The mRNA expressions of IL-23p19, IL-12p40, and IL-17 in reticular OLP lesions (n = 14) and normal oral mucosa tissues (n = 10). All data were shown as mean ± SEM.  **P < 0.01;  **P < 0.05; NS: nonsignificantly.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4121042&req=5

fig2: Expressions of IL-23 and IL-17 in OLP lesions. (a) The average staining scores of IL-23p19 in erosive OLP lesions (n = 13), reticular OLP lesions (n = 14), and normal oral mucosa tissues (n = 10). (b) The average number of IL-17+ cells per hpf in erosive OLP lesions (n = 13), reticular OLP lesions (n = 14), and normal oral mucosa tissues (n = 10). ((c) and (d)) The mRNA expressions of IL-23p19, IL-12p40, and IL-17 in reticular OLP lesions (n = 14) and normal oral mucosa tissues (n = 10). All data were shown as mean ± SEM.  **P < 0.01;  **P < 0.05; NS: nonsignificantly.
Mentions: To identify whether IL-23/IL-17 is involved in the local pathogenesis of OLP, we firstly detected the expression and distribution of IL-23 p19, a unique subunit of IL-23, and IL-17 in OLP lesions and NOM tissues. Using IHC detection, we observed diffuse and strong expressions of IL-23p19 in both erosive and reticular OLP lesions. The positive staining of IL-23p19 predominantly concentrated on the epithelium of OLP lesions and also on the extracellular matrix of the lamina propria (Figures 1(a)–1(d)). In contrast, only a few keratinocytes in the epidermis layer of the NOM tissues showed weak stain of IL-23p19 (Figures 1(e) and 1(f)). Moreover, we found abundant IL-17 positive stainings on the cytoplasm of the infiltrated lymphocytes in the lesions of both erosive and reticular OLP, but only a few sporadic IL-17+ cells in the normal oral mucosa (Figures 1(g)–1(l)). The statistical data showed that both the erosive and reticular OLP lesions had significantly increased immunostaining scores of IL-23p19, as well as the numbers of IL-17+ cells, compared to the normal oral mucosa. In addition, erosive OLP lesions contained a significantly increased number of IL-17+ cells compared to the reticular OLP lesions. However, there is no significant difference in IL-23p19 staining score between erosive and the reticular OLP lesions (Figures 2(a) and 2(b)).

Bottom Line: In addition, the expressions of IL-23 and IL-17 are positively correlated in reticular OLP tissues.Results from in vitro studies revealed that exogenous IL-23 could increase the percentage of Th17 cells and IL-17 production in the CD4+T cells from reticular OLP patients.Furthermore, we also found that exogenous IL-17 could significantly enhance the mRNA expressions of β-defensin-2, -3, CCL-20, IL-8, and TNF-α, but not β-defensin-1, CXCL-9, -10, -11, CCL-5, and IL-6 in human oral keratinocytes.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu 610041, China ; The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, No. 237 Luoyu Road, Wuhan 430079, China.

ABSTRACT
Interleukin- (IL-) 23/IL-17 axis is a newly discovered proinflammatory signaling pathway and has been implicated in the pathogenesis of many chronic inflammatory and immune disorders. Here we investigated whether the IL-23/IL-17 axis was present and functional in the lesions of oral lichen planus (OLP), a chronic inflammatory disease affecting the oral mucosa. Using immunohistochemistry and quantitative PCR, we found that the subunits of IL-23 and IL-17 were overexpressed in OLP lesions than in normal oral mucosa tissues. In addition, the expressions of IL-23 and IL-17 are positively correlated in reticular OLP tissues. Results from in vitro studies revealed that exogenous IL-23 could increase the percentage of Th17 cells and IL-17 production in the CD4+T cells from reticular OLP patients. Furthermore, we also found that exogenous IL-17 could significantly enhance the mRNA expressions of β-defensin-2, -3, CCL-20, IL-8, and TNF-α, but not β-defensin-1, CXCL-9, -10, -11, CCL-5, and IL-6 in human oral keratinocytes. Taken together, our results revealed an overexpression pattern and selectively regulatory roles of IL-23/IL-17 axis in the OLP lesions, suggesting that it may be a pivotal regulatory pathway in the complex immune network of OLP lesions.

Show MeSH
Related in: MedlinePlus