PMID- 25089120
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140804
LR  - 20211021
IS  - 1476-9255 (Print)
IS  - 1476-9255 (Electronic)
IS  - 1476-9255 (Linking)
VI  - 11
DP  - 2014
TI  - Role of toll-like receptors in human iris pigment epithelial cells and their 
      response to pathogen-associated molecular patterns.
PG  - 20
LID - 10.1186/1476-9255-11-20 [doi]
AB  - BACKGROUND: Toll-like receptor (TLR) activation is hypothesized to contribute to 
      inflammatory eye disease including uveitis, yet the distribution pattern of TLRs 
      in human uveal tissues remains poorly described. The purpose of this study was to 
      investigate the expression profile of TLRs in human iris pigment epithelial cells 
      (IPE) at the gene and protein level and examine the effect of pathogen-associated 
      molecular patterns (PAMPs), such as Pam3CSK4.3HCl, Poly(I:C), lipopolysaccharides 
      (LPS from E. coli serotype O111:B4), Flagellin, MALP-2 (macrophage activating 
      lipopeptide-2), Poly(U) and CpGODN2395 on the production of inflammatory 
      mediators including interleukin-8 (IL-8) and monocyte chemotactic protein 1 
      (MCP-1) from human IPE and retinal pigment epithelial cells (RPE). METHODS: 
      RT-PCR and Western blotting was employed to investigate the expression of TLRs 
      1-10 in primary IPE and RPE. Secretion of IL-8 or MCP-1 following treatment with 
      PAMPs was measured by ELISA. The role of TLR2, TLR3 and TLR4 in mediating an 
      inflammatory response was investigated using pharmacological TLR inhibitors. 
      RESULTS: IPE and RPE expressed transcripts for TLR1-6 and 8-10; and proteins for 
      TLR1-6 and 9. IPE secreted IL-8 or MCP-1 in response to Pam3CSK4.3HCl, Poly(I:C), 
      LPS and MALP-2, whereas RPE produced IL-8 only after Poly(I:C), LPS or MALP-2 
      treatment. TLR inhibitors (OxPAPC, CI-095 and chloroquine) blocked IL-8 secretion 
      in Poly(I:C), LPS or MALP-2-treated IPE and RPE. CONCLUSIONS: Ocular pigment 
      epithelial cells respond to PAMPs through activation of TLRs, particularly TLR2, 
      TLR3 and TLR4. Expression of TLRs in human IPE cells provides a basis for 
      responses to many ocular pathogens and their activation may be involved in the 
      pathogenesis of ocular inflammation.
FAU - Mai, Kelly
AU  - Mai K
AD  - Inflammation and Infection Research Centre, Department of Pathology, School of 
      Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, 
      Australia.
FAU - Chui, Jeanie Jy
AU  - Chui JJ
AD  - Inflammation and Infection Research Centre, Department of Pathology, School of 
      Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, 
      Australia ; Department of Ophthalmology, Prince of Wales Hospital, Randwick, NSW, 
      Australia.
FAU - Di Girolamo, Nick
AU  - Di Girolamo N
AD  - Inflammation and Infection Research Centre, Department of Pathology, School of 
      Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, 
      Australia.
FAU - McCluskey, Peter J
AU  - McCluskey PJ
AD  - Save Sight Institute, Sydney Eye Hospital, University of Sydney, Sydney, 
      Australia.
FAU - Wakefield, Denis
AU  - Wakefield D
AD  - Inflammation and Infection Research Centre, Department of Pathology, School of 
      Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, 
      Australia ; UNSW Medicine, University of New South Wales, Sydney, Australia.
LA  - eng
PT  - Journal Article
DEP - 20140716
PL  - England
TA  - J Inflamm (Lond)
JT  - Journal of inflammation (London, England)
JID - 101232234
PMC - PMC4118659
OTO - NOTNLM
OT  - IPE
OT  - Immunology
OT  - PAMPs
OT  - TLR
OT  - Uveitis
EDAT- 2014/08/05 06:00
MHDA- 2014/08/05 06:01
PMCR- 2014/07/16
CRDT- 2014/08/05 06:00
PHST- 2013/10/14 00:00 [received]
PHST- 2014/07/05 00:00 [accepted]
PHST- 2014/08/05 06:00 [entrez]
PHST- 2014/08/05 06:00 [pubmed]
PHST- 2014/08/05 06:01 [medline]
PHST- 2014/07/16 00:00 [pmc-release]
AID - 1476-9255-11-20 [pii]
AID - 10.1186/1476-9255-11-20 [doi]
PST - epublish
SO  - J Inflamm (Lond). 2014 Jul 16;11:20. doi: 10.1186/1476-9255-11-20. eCollection 
      2014.