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Int Immunopharmacol. 2016 Nov;40:392-399. doi: 10.1016/j.intimp.2016.09.027. Epub 2016 Sep 30.

LOX-1 and TLR4 affect each other and regulate the generation of ROS in A. fumigatus keratitis.

Author information

1
Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
2
Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China. Electronic address: zhaoguiqiu_good@126.com.

Abstract

PURPOSE:

To explore the relationship between LOX-1 and TLR4 in Aspergillus fumigatus (A. fumigatus) keratitis. To determine LOX-1 and TLR4 can affect each other and regulate inflammation through regulation of the generation of reactive oxygen species (ROS) in A. fumigatus keratitis.

METHODS:

The cornea and abdominal cavity extracted neutrophils of susceptible C57BL/6 mice were infected with A. fumigatus. The cornea and neutrophils were pretreated with LOX-1 neutralizing antibody, Polyinosinic acid (Poly(I)) (the inhibitor of LOX-1) or CLI-095 (the inhibitor of TLR4) separately before infection. LOX-1, TLR4 and IL-1β expression were detected in normal and infected cornea by PCR and Western Blot, while ROS was detected in the neutrophils by flow cytometry.

RESULTS:

LOX-1, TLR4, IL-1β mRNA and protein levels were up-regulated in C57BL/6 cornea after infection. LOX-1 neutralizing antibody or Poly(I) pretreatment decreased the expression of LOX-1, TLR4 and IL-1β in C57BL/6 cornea after infection and CLI-095 pretreatment decreased the expression of LOX-1, TLR4 and IL-1β in C57BL/6 cornea after infection. ROS generation was increased in C57BL/6 neutrophils after infection, however, ROS generation was decreased in C57BL/6 neutrophils after infection by LOX-1 neutralizing antibody or Poly(I) or CLI-095 pretreatment.

CONCLUSION:

LOX-1, TLR4 and IL-1β expression and ROS generation are increased after infection. LOX-1 and TLR4 can affect each other and regulate the generation of ROS in A. fumigatus keratitis. Inhibition of LOX-1 and TLR4 can reduce ROS generation.

KEYWORDS:

Aspergillus fumigatus; Keratitis; LOX-1; ROS; TLR4

PMID:
27694040
DOI:
10.1016/j.intimp.2016.09.027
[Indexed for MEDLINE]

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