Glucocorticoids inhibit the innate immune system of human corneal fibroblast through their suppression of toll-like receptors

[摘要] Purpose: To evaluate the effect ofglucocorticoids on the expression and function of Toll-like receptors(TLRs) in human corneal fibroblasts (HCFs). Methods: Cultured HCF cells werestimulated with three different concentrations of hydrocortisone. Theeffect on the expression of TLR2 and TLR4 wasdetermined by real-time PCR. The TLR2, TLR4, and pIκB-α proteins werecompared by western blot. The release of IL-6 and IL-8 was measuredusing enzyme-linked immunosorbent assay in the presence and absence ofTLR2 and TLR4-specific blocking antibodies. Results: Incubation of HCFs withhydrocortisone markedly inhibited the expression of TLR2 and TLR4mRNAs and decreased the release of IL-6 and IL-8 in a dose-dependentmanner. Western blot analysis confirmed that expression of TLR2, TLR4,and pIκB-α was also downregulated in response to hydrocortisone. Theresult of ELISA also showed the release of IL-6 and IL-8 can also beinhibited by hydrocortisone. However, all these inhibitions werecounteracted after pretreatment with anti-TLR2 and anti-TLR4 monoclonalantibodies. Conclusions: Glucocorticoids, such ashydrocortisone, can inhibit the expression of TLR2 and TLR4 on HCFs,and thus may increase susceptibility to cornea infections. Our resultssuggest that topical glucocorticoids may affect the cornea’s innateimmunity through TLRs.

[学科分类] 生物化学/生物物理