Growth hormone-releasing hormone receptor mediates cytokine production in ciliary and iris epithelial cells during LPS-induced ocular inflammation

Jia Lin Ren, Qiu Xiao Yu, Ding Ma, Wei Cheng Liang, Pui Ying Leung, Tsz Kin Ng, Wai Kit Chu, Andrew V Schally, Chi Pui Pang, Sun On Chan

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The receptor for growth hormone-releasing hormone (GHRH-R) has been shown to upregulate specifically in the ciliary and iris epithelial cells and infiltrating cells in the aqueous humor in a rat model of acute anterior uveitis. Treatment with GHRHR-R antagonist alleviates significantly these inflammatory responses. Herein we investigated whether the ciliary and iris epithelial cells can respond directly to lipopolysaccharide (LPS) without the influences of circulating leukocytes to produce inflammatory mediators through a GHRH-R mediated mechanism. In explant cultures of rat ciliary body and iris, LPS caused a substantial increase of GHRH-R in 24 h. Immunohistochemistry showed a localization of TLR4, the receptor for LPS, and an elevated expression of IL-6 and IL-1β in ciliary and iris epithelial cells after LPS treatment. LPS also elevated the level of IL-1β, IL-6, and iNOS and increased secretion of IL-1β and IL-6 from the explants. The GHRH-R antagonist, MIA-602, suppressed the elevated expression of IL-1β and IL-6, and reduced the release of IL-6. Such effects were not seen for the GHRHR agonist, MR-409. When co-cultured with leukocytes, expression of GHRH-R in the ocular explants was further enhanced during LPS treatment. Our results demonstrate a direct action of LPS on ciliary and iris epithelial cells to produce pro-inflammatory factors through a GHRH-R mediated mechanism, and suggest a role of these epithelial cells, in addition to the resident antigen presenting cells, in immune surveillance of the eye. Infiltrating leukocytes may enhance these inflammatory responses by regulating GHRH-R in ciliary and iris epithelial cells, in addition to their functions of synthesizing proinflammatory cytokines.

Original languageEnglish (US)
Pages (from-to)277-284
Number of pages8
JournalExperimental Eye Research
Volume181
DOIs
StatePublished - Apr 1 2019

Keywords

  • Ciliary body
  • Eye
  • GHRH-R
  • Iris
  • Leukocyte
  • Uveitis

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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