Novel production of interleukin-1 receptor antagonist peptides in normal human cornea

Michael C. Kennedy, James T. Rosenbaum, Jeffrey Brown, Stephen R. Planck, Xiaona Huang, Cheryl A. Armstrong, John C. Ansel

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Interleukin-1 receptor antagonist (IL-1ra) is an important modulator of IL-1 activity in a variety of tissues. IL-1ra is differentially produced by different cell types as a 22-26-kD secreted peptide (sIL-1ra) and/or a smaller 16- or 18-kD intracellular peptide (icIL-1ra). This study was undertaken to evaluate the production of IL-1ra in the human cornea. IL-1ra mRNA can be detected in early passage human corneal epithelial cells and corneal stromal fibroblasts and is significantly enhanced by IL-1. Corneal endothelial cells do not express IL-1ra mRNA. Immunohistochemical studies of cultured corneal cells and whole human cornea demonstrate IL-1ra protein production by both the epithelial and stromal cells but not the endothelial cells. Reverse transcriptase polymerase chain reaction, ELISA, and immunoprecipitation studies indicate that corneal epithelial cells are capable of producing both icIL-1ra and sIL-1ra forms of IL-1ra whereas the corneal stromal cells produce only icIL-1ra. In addition to the larger 18-kD icIL-1ra, both corneal epithelial and stromal cells are also capable of producing a smaller recently described 16-kD icIL-1ra. Thus, the differential production of IL-1ra in the human cornea is unique; whereas both epithelial and stromal cells produce icIL-1ra (type 1 and type 2), the epithelial cells appear to also produce sIL-1ra. It is proposed that these IL-1ra proteins may play an important role in regulating IL-1-induced corneal inflammation.

Original languageEnglish (US)
Pages (from-to)82-88
Number of pages7
JournalJournal of Clinical Investigation
Volume95
Issue number1
DOIs
StatePublished - Jan 1995

Keywords

  • corneal epithelial cells
  • corneal inflammation
  • corneal stromal fibroblasts
  • interleukin-1
  • secreted interleukin-1 receptor antagonist

ASJC Scopus subject areas

  • Medicine(all)

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