September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Contrary effects of Interleukin-1 receptor antagonist (Ra) and IL-36Ra on corneal innate immune defense against Pseudomonas aeruginosa keratitis.
Author Affiliations & Notes
  • Nan Gao
    Wayne State Univ/Kresge Eye Inst, Detroit, Michigan, United States
  • Fushin X Yu
    Wayne State Univ/Kresge Eye Inst, Detroit, Michigan, United States
  • Theodore J. Standiford
    Pulmonary and Critical Care Medicine, Ann Arbor, Michigan, United States
  • Footnotes
    Commercial Relationships   Nan Gao, None; Fushin Yu, None; Theodore J. Standiford, None
  • Footnotes
    Support  NIH grants R01 EY017960, EY010869
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Nan Gao, Fushin X Yu, Theodore J. Standiford; Contrary effects of Interleukin-1 receptor antagonist (Ra) and IL-36Ra on corneal innate immune defense against Pseudomonas aeruginosa keratitis.. Invest. Ophthalmol. Vis. Sci. 201657(12):.

      Download citation file:


      © 2017 Association for Research in Vision and Ophthalmology.

      ×
  • Supplements
Abstract

Purpose : To elucidate the role of IL-1Ra and IL-36Ra in controlling corneal inflammation and innate immunity in C47BL/6 mouse model of Pseudomonas aeruginosa keratitis.

Methods : Scarified B6 mouse corneas inoculated with 104 P. aeruginosa. At 6 hpi, epithelial cells were scraped off the cornea and IL-36α, β, γ, and IL36Ra expressions were detected by PCR. To determine the role of IL-1 and IL-36 signaling in P. aeruginosa keratitis, the corneas of B6 mouse corneas were treated with siRNA of IL-1Ra or IL-36Ra or recombinant IL-36γ, followed by P. aeruginosa inoculation. Disease progress was monitored by digital photograph, clinical scoring, and MPO measurement for PMN infiltration. The expressions of various pro-inflammatory and innate defense gene were determined by real-time PCR.

Results : P. aeruginosa infection induced the expressions of IL-1β, IL-1Ra, IL-36α and IL-36γ, but not IL-36β and IL-36Ra in mouse CECs. While downregulation of IL-1Ra greatly increased severity of keratitis, IL-36Ra siRNA treatment protected B6 mouse corneas from P. aeruginosa infection, including markedly decreases in bacterial burden and PMN infiltration. Knockdown IL-36Ra induce upregulation AMPs while IL-1RA Knockdown downregulate the expression of AMPs. Topical application of IL-36γ ameliorated P. aeruginosa keratitis, downregulate and up-regulated defensing-3, s100a8 and ISG15 expression in the cornea.

Conclusions : IL-36 is induced during infection in the cornea, where it promotes bacterial clearance and regulates the appropriateness and intensity of innate immune responses. Topical IL-36 + IL-1Ra may be used prophylactically post ocular surgery or as an adjunctive therapy to treat microbial keratitis.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×