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Published on: January 14, 2011
β-Glucan augments IL-1β production by activating the JAK2/STAT3 pathway in cultured rabbit keratinocytes
Wudian Xiao1, Lu Fu2, Congwei Gu2
1Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Laboratory Animal Center, Southwest Medical University, Luzhou, 646000, China.
Abstract:
Trichophyton mentagrophytes (T. mentagrophytes) is the main cause of rabbit dermatophytosis. As the main pathogen-associated molecular pattern of T. mentagrophytes, the role of β-glucan in the pathogenesis of rabbit dermatophytosis remains elusive. Keratinocytes (KC) are the main cellular component and the first defensive line against fungal pathogens in the skin. Therefore, the present study investigated the effects of β-glucan on rabbit KC from dorsal skin. β-glucan was found to inhibit KC proliferation by 10% at 20 ug/ml and this concentration was thus considered as optimal. Next, 20 ug/ml β-glucan stimulation for 24 h significantly increased CXCL8, CXCL11, and IL-1β secretions in KC. Furthermore, β-glucan exposure induced the expressions of JAK2 mRNA, STAT3 mRNA, and p-STAT3 protein. Silencing JAK2 expression inhibited p-STAT3 protein expression and β-glucan-induced IL-1β secretion. And overexpression of JAK2 further promoted β-glucan-mediated p-STAT3 protein and IL-1β productions. These results suggested that β-glucan-induced CXCL8, CXCL11, and IL-1β secretions in rabbit KC might be involved in the inflammatory response of T. mentagrophytes infected rabbit dorsal skin. However, only IL-1β secretion was promoted by the JAK2/STAT3 signaling pathway. In conclusion, this study is a necessary step toward elucidating the mechanisms that underlie skin immune system injury stimulated by β-glucan.
Insights
Beta-glucan, a key component of Trichophyton mentagrophytes, triggers inflammatory responses in rabbit skin keratinocytes. This study reveals beta-glucan
Area of Science:
- Veterinary Dermatology
- Immunology
- Mycology
Background:
- Trichophyton mentagrophytes (T. mentagrophytes) is a primary cause of dermatophytosis in rabbits.
- Beta-glucan is a major pathogen-associated molecular pattern of T. mentagrophytes, but its role in rabbit skin infections is not well understood.
- Keratinocytes (KC) are crucial skin cells and the initial defense against fungal invasion.
Purpose of the Study:
- To investigate the effects of beta-glucan on rabbit keratinocytes (KC).
- To elucidate the role of the JAK2/STAT3 signaling pathway in beta-glucan-induced immune responses in rabbit KC.
Main Methods:
- Rabbit KC were treated with beta-glucan at varying concentrations.
- Cell proliferation was assessed, and optimal beta-glucan concentration (20 ug/ml) was determined.
- Secretions of CXCL8, CXCL11, and IL-1β were measured.
- Expressions of JAK2 mRNA, STAT3 mRNA, and p-STAT3 protein were analyzed.
- JAK2 silencing and overexpression experiments were conducted to study pathway involvement.
Main Results:
- Beta-glucan (20 ug/ml) inhibited KC proliferation by 10% and significantly increased CXCL8, CXCL11, and IL-1β secretions.
- Beta-glucan induced the expression of JAK2 mRNA, STAT3 mRNA, and p-STAT3 protein.
- JAK2/STAT3 signaling pathway was found to mediate beta-glucan-induced IL-1β secretion, but not CXCL8 or CXCL11.
Conclusions:
- Beta-glucan stimulates rabbit KC to secrete inflammatory cytokines CXCL8, CXCL11, and IL-1β.
- The JAK2/STAT3 pathway is specifically involved in mediating beta-glucan-induced IL-1β production.
- This study provides insights into the mechanisms of skin immune system injury caused by beta-glucan in rabbit dermatophytosis.
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