PMID- 27918831
OWN - NLM
STAT- MEDLINE
DCOM- 20170615
LR  - 20220129
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 57
IP  - 15
DP  - 2016 Dec 1
TI  - Induction of Chemokine Secretion and Monocyte Migration by Human Choroidal 
      Melanocytes in Response to Proinflammatory Cytokines.
PG  - 6568-6579
LID - 10.1167/iovs.15-18524 [doi]
AB  - PURPOSE: To determine to which extent inflammatory cytokines affect chemokine 
      secretion by primary human choroidal melanocytes (HCMs), their capacity to 
      attract monocytes, and whether HCMs are able to influence the proliferation of 
      activated T cells. METHODS: Primary cultures of HCMs were established from eyes 
      of 13 donors. Human choroidal melanocytes were stimulated with IFN-gamma and TNF-alpha or 
      with supernatant from activated T cells (T-cell-conditioned media [TCM]). Gene 
      expression analysis was performed by using microarrays. Protein levels were 
      quantified with ELISA or cytometric bead array. Supernatants of HCMs were 
      assessed for the capability to attract monocytes in a transwell plate. 
      Proliferation of activated T cells was assessed in a direct coculture with HCMs 
      by a [3H]-thymidine incorporation assay. RESULTS: Stimulation of HCMs with TCM or 
      IFN-gamma and TNF-alpha resulted in increased expression and secretion of CXCL8, CXCL9, 
      CXCL10, CXCL11, CCL2, CCL5 and intercellular adhesion molecule 1. Vascular 
      endothelial growth factor and monocyte migration inhibitory factor were 
      constitutively expressed without changes in response to proinflammatory 
      cytokines. Supernatants derived from unstimulated cultures of 10 HCM donors 
      induced a high initial level of monocyte migration, which decreased upon 
      stimulation with either TCM or IFN-gamma and TNF-alpha. The supernatants from three HCM 
      donors initially showed a low level of monocyte attraction, which increased after 
      exposure to proinflammatory cytokines. Direct coculture of HCMs with T cells 
      resulted in inhibition of T-cell proliferation. CONCLUSIONS: These results showed 
      that normal and activated HCMs are immunologically active by secreting 
      chemokines, and that HCMs are able to attract monocytes in addition to inhibiting 
      T-cell proliferation.
FAU - Jehs, Tina
AU  - Jehs T
AD  - University of Copenhagen, Department of Immunology and Microbiology, Eye Research 
      Unit, Copenhagen, Denmark.
FAU - Faber, Carsten
AU  - Faber C
AD  - University of Copenhagen, Department of Immunology and Microbiology, Eye Research 
      Unit, Copenhagen, Denmark.
FAU - Udsen, Maja S
AU  - Udsen MS
AD  - University of Copenhagen, Department of Immunology and Microbiology, Eye Research 
      Unit, Copenhagen, Denmark.
FAU - Jager, Martine J
AU  - Jager MJ
AD  - Department of Ophthalmology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Clark, Simon J
AU  - Clark SJ
AD  - Centre for Ophthalmology and Vision Sciences, Institute of Human Development, AV 
      Hill Building, University of Manchester, Manchester, United Kingdom.
FAU - Nissen, Mogens H
AU  - Nissen MH
AD  - University of Copenhagen, Department of Immunology and Microbiology, Eye Research 
      Unit, Copenhagen, Denmark.
LA  - eng
GR  - MR/K024418/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Chemokine CXCL9)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - Uveal melanoma
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Chemokine CXCL9/*metabolism
MH  - Choroid/metabolism/*pathology
MH  - Culture Media, Conditioned
MH  - Cytokines/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Humans
MH  - Melanocytes/*pathology
MH  - Melanoma/metabolism/*pathology
MH  - Middle Aged
MH  - Monocytes/*pathology
MH  - Photomicrography
MH  - Tumor Cells, Cultured
MH  - Uveal Neoplasms/metabolism/*pathology
MH  - Young Adult
EDAT- 2016/12/06 06:00
MHDA- 2017/06/16 06:00
CRDT- 2016/12/06 06:00
PHST- 2016/12/06 06:00 [entrez]
PHST- 2016/12/06 06:00 [pubmed]
PHST- 2017/06/16 06:00 [medline]
AID - 2589963 [pii]
AID - 10.1167/iovs.15-18524 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2016 Dec 1;57(15):6568-6579. doi: 
      10.1167/iovs.15-18524.