PMID- 32663289
OWN - NLM
STAT- MEDLINE
DCOM- 20210107
LR  - 20210107
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 61
IP  - 8
DP  - 2020 Jul 1
TI  - Retinoic Acid Potentiates Orbital Tissues for Inflammation Through NF-kappaB and 
      MCP-1.
PG  - 17
LID - 10.1167/iovs.61.8.17 [doi]
LID - 17
AB  - PURPOSE: The orbit displays unique vulnerability to inflammatory conditions. The 
      most prevalent of these conditions, thyroid eye disease (TED), occurs in up to 
      50% of patients with Graves' disease (GD). Whereas the pathology of both TED and 
      GD is driven by autoantibodies, it is unclear why symptoms manifest specifically 
      in the orbit. METHODS: We performed retinoic acid treatment on both normal and 
      TED patient-derived orbital fibroblasts (OFs) followed by mRNA and protein 
      isolation, quantitative real-time polymerase chain reaction (qRT-PCR), 
      enzyme-linked immunosorbent assay, RNA sequencing, and Western blot analyses. 
      RESULTS: Both normal and TED patient-derived OFs display robust induction of 
      monocyte chemoattractant protein 1 (MCP-1) upon retinoid treatment; TED OFs 
      secrete significantly more MCP-1 than normal OFs. In addition, pretreatment of 
      OFs with thiophenecarboxamide (TPCA-1) inhibits retinoid-induced MCP-1 induction, 
      suggesting an NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B 
      cells)-dependent mechanism. We also found that treatment with cholecalciferol 
      (vitamin D3) mitigates MCP-1 induction, likely because of competition between 
      retinoic acid receptors (RARs) and vitamin D receptors (VDR) for their common 
      binding partner retinoid nuclear receptors (RXRs). CONCLUSIONS: Retinoids that 
      naturally accumulate in orbital adipose tissue can act on orbital fibroblasts to 
      induce the expression of inflammation-associated genes. These data suggest a 
      potential role for retinoids in sensitizing the orbit to inflammation.
FAU - Unsworth, Shelby P
AU  - Unsworth SP
AD  - ,.
FAU - Heisel, Curtis J
AU  - Heisel CJ
AD  - ,.
FAU - Tingle, Christina F
AU  - Tingle CF
AD  - ,.
FAU - Rajesh, Niharika
AU  - Rajesh N
AD  - ,.
FAU - Kish, Phillip E
AU  - Kish PE
AD  - ,.
FAU - Kahana, Alon
AU  - Kahana A
AD  - ,.
AD  - ,.
LA  - eng
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 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis/*genetics
MH  - Fibroblasts/metabolism/pathology
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Inflammation/*genetics/metabolism/pathology
MH  - NF-kappa B/biosynthesis/*genetics
MH  - Orbit/metabolism/pathology
MH  - RNA, Messenger/*genetics
MH  - Signal Transduction
MH  - Tretinoin/*pharmacology
PMC - PMC7425727
COIS- Disclosure: S.P. Unsworth, None; C.J. Heisel, None; C.F. Tingle, None; N. Rajesh, 
      None; P.E. Kish, None; A. Kahana, None
EDAT- 2020/07/15 06:00
MHDA- 2021/01/08 06:00
PMCR- 2020/07/14
CRDT- 2020/07/15 06:00
PHST- 2020/07/15 06:00 [entrez]
PHST- 2020/07/15 06:00 [pubmed]
PHST- 2021/01/08 06:00 [medline]
PHST- 2020/07/14 00:00 [pmc-release]
AID - 2770311 [pii]
AID - IOVS-20-29843 [pii]
AID - 10.1167/iovs.61.8.17 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2020 Jul 1;61(8):17. doi: 10.1167/iovs.61.8.17.