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Jing Lin, Guiqiu Zhao, Qian Wang; Interleukin-32 induced thymic stromal lymphopoietin plays a critical role in the inflammatory response of Human Corneal Epithelium. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4361. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Interleukin (IL)-32 is a newly discovered cytokine and has been associated with a variety of inflammatory diseases. Thymic stromal lymphopoietin (TSLP) plays important roles in mucosal epithelial cells, especially in allergy-induced inflammation, through the TSLP-TSLPR(Thymic stromal lymphopoietin receptor) signaling pathway. However, the relationship between IL-32 and TSLP in the ocular surface remains unclear. This study sought to identify the relationship and function of IL-32 and TSLP in regulating the pro-inflammatory cytokine production in corneal epithelial cells.
Human corneal tissues and cultured primary human corneal epithelial cells (HCECs) were treated with different IL-32 concentrations, in the presence or absence of various inhibitors to evaluate TSLP expression and localization and the signaling pathways involved in regulating pro-inflammatory cytokine production. TSLP mRNA expression was determined by reverse transcription and real time PCR, and protein production was measured by ELISA and immunohistochemical staining.
TSLP protein expression was examined in donor corneal epithelium. IL-32 significantly stimulated TSLP and pro-inflammatory cytokines (TNFα and IL-6) production in HCECs at both mRNA and protein levels. The production of pro-inflammatory mediators by IL-32 was increased by recombinant TSLP protein. Interestingly, the NF-κB inhibitor quinazoline and the caspase-1 inhibitor VX-765 suppressed IL-32 induced pro-inflammatory cytokines production (TNFα and IL-6).
These findings demonstrate that IL-32 and IL-32 -induced TSLP are important cytokines involved in inflammatory responses through caspase-1 and NF-κB signaling pathways, in human corneal epithelium, suggesting novel molecular targets in the inflammatory diseases of the ocular surface.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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