The production mechanism and immunosuppression effect of pulmonary surfactant protein D via toll like receptor 4 signaling pathway in human corneal epithelial cells during Aspergillus fumigatus infection

Xian Wu, Guiqiu Zhao, Jing Lin, Nan Jiang, Cui Li, Liting Hu, Xudong Peng, Qiang Xu, Qian Wang, Hui Li, Yan Zhang

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Objective To observe the production mechanism of surfactant protein D (SP-D) in human corneal epithelial cells (HCECs) when infected by Aspergillus fumigatus (A. fumigatus) hyphae, and explore whether SP-D can inhibit the cell activations through toll-like receptor 4 signaling pathway during fungal infection. Methods mRNA and protein expressions of SP-D were evaluated in HCECs after stimulation by A. fumigatus, with or without pretreatment of TLR4 inhibitor (CLI-095) by real time PCR and Western blot. The expression levels of inflammatory cytokines IL-1β and IL-8 evaluated when pretreated with SP-D antibody or recombinant human SP-D in fungi-stimulated HCECs by real time PCR and ELISA, IL-1β and IL-8 expressions were also detected in A. fumigatus-stimulated HCECs that pretreated with CLI095 or MyD88 inhibitor (Pepinh-MYD) and recombinant human SP-D. Results mRNA and protein levels of SP-D increased after stimulation of A. fumigatus for 16 h and 20 h respectively. The upregulation of SP-D could be inhibited by CLI-095. mRNA and protein expressions of IL-1β and IL-8 decreased significantly when pretreated HCECs with recombinant human SP-D for 4 h before A. fumigatus stimulation, while IL-1β and IL-8 increased when pretreated with SP-D antibody for 1 h. Pretreatment of CLI095 or Pepinh-MYD can increase the expressions of IL-1β and IL-8 mRNA and protein in HCECs induced by recombinant human SP-D and A. fumigatus. Conclusions SP-D can be stimulated by TLR4 during A. fumigatus infection. Recombinant human SP-D can inhibit the expression of inflammatory cytokines through TLR4 signaling pathway.

Original languageEnglish
Pages (from-to)433-439
Number of pages7
JournalInternational Immunopharmacology
Volume29
Issue number2
DOIs
StatePublished - 1 Dec 2015
Externally publishedYes

Keywords

  • Aspergillus fumigatus
  • Fungal keratitis
  • Surfactant protein D
  • Toll-like receptor 4

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