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Retinoic Acid Potentiates Orbital Tissues for Inflammation Through NF-?B and MCP-1.

ABSTRACT: 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-?B (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.

SUBMITTER: Unsworth SP

PROVIDER: S-EPMC7425727 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Retinoic Acid Potentiates Orbital Tissues for Inflammation Through NF-κB and MCP-1.

Unsworth Shelby P SP Heisel Curtis J CJ Tingle Christina F CF Rajesh Niharika N Kish Phillip E PE Kahana Alon A

Investigative ophthalmology & visual science 20200701 8

<h4>Purpose</h4>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.<h4>Methods</h4>We performed retinoic acid treatment on both normal and TED patient-derived orbital fibroblasts (OFs) followed by mRNA and protein isolation, ...[more]

PMID: 32663289

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Retinoic Acid Potentiates Orbital Tissues for Inflammation Through NF-?B and MCP-1.

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Retinoic Acid Potentiates Orbital Tissues for Inflammation Through NF-κB and MCP-1.

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