Localization and gene expression of human beta-defensin 9 at the human ocular surface epithelium
| Autor: | Harminder S Dua, Peng Chen, Bina Kulkarni, Hanif Suleman, Ahmad Muneer Otri, Imran Mohammed, Andrew Hopkinson |
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| Rok vydání: | 2010 |
| Předmět: |
beta-Defensins
Interleukin-1beta Nod2 Signaling Adaptor Protein Down-Regulation Gene Expression Inflammation Biology Limbus Corneae Proinflammatory cytokine Downregulation and upregulation NOD2 Nod1 Signaling Adaptor Protein Gene expression medicine Humans RNA Messenger Receptor Defensin Cell Line Transformed Innate immune system Tumor Necrosis Factor-alpha Toll-Like Receptors Epithelium Corneal Epithelial Cells Cell biology Immunology sense organs medicine.symptom Conjunctiva |
| Zdroj: | Investigative ophthalmologyvisual science. 51(9) |
| ISSN: | 1552-5783 |
| Popis: | PURPOSE. Antimicrobial peptides (AMPs) are multifunctional host defense molecules. Human -defensin 9 (HBD9) has previously been shown to be downregulated during ocular surface (OS) infection or inflammation. Here, the authors aimed to study localization of HBD9 protein in different OS regions and to determine the role of Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors, and proinflammatory cytokines in HBD9 expression. METHODS. Immunolocalization of HBD9 protein was carried out on the normal human OS regions (cornea, limbus, and conjunctiva). Quantitative PCR analysis of HBD9 mRNA was performed in SV40-transformed human corneal epithelial cells (hCECs) treated for different durations with synthetic pathogen-associated molecular patterns (PAMPs) and recombinant cytokines. RESULTS. HBD9 protein was constitutively expressed on OS epithelia. Corneal and limbal epithelia and corneal stroma demonstrated modest levels of HBD9, whereas conjunctival epithelium demonstrated high levels of HBD9 protein. TLR02, TLR03, TLR04, and TLR05 were shown to modulate HBD9 mRNA in hCECs. Similarly, NOD2 and IL-1 were also shown to alter HBD9 in a time-dependent manner. In response to infection-related PAMPs and inflammatory cytokines, an initial increase in HBD9 mRNA levels was observed, followed by a significant downregulation. CONCLUSIONS. This is the first demonstration of HBD9 protein expression at different OS regions. The authors also determined the role of various innate immune receptors in HBD9 mRNA modulation. Further understanding of the signaling mechanisms involved in the initial response of HBD9 to infection or inflammation is likely to indicate future therapeutic directions with this AMP. (Invest Ophthalmol Vis Sci. 2010;51: 4677‐4682) DOI:10.1167/iovs.10-5334 |
| Databáze: | OpenAIRE |
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