論文 - 詳細
| RRC ID | 58733 |
|---|---|
| 著者 | Fu R, Guo H, Janga S, Choi M, Klinngam W, Edman MC, Hamm-Alvarez SF. |
| タイトル | Cathepsin S activation contributes to elevated CX3CL1 (fractalkine) levels in tears of a Sjögren's syndrome murine model. |
| ジャーナル | Sci Rep |
| Abstract |
Autoimmune dacryoadenitis and altered lacrimal gland (LG) secretion are features of Sjögren's syndrome (SS). Activity of cathepsin S (CTSS), a cysteine protease, is significantly and specifically increased in SS patient tears. The soluble chemokine, CX3CL1 (fractalkine), is cleaved from membrane-bound CX3CL1 by proteases including CTSS. We show that CX3CL1 is significantly elevated by 2.5-fold in tears (p = 0.0116) and 1.4-fold in LG acinar cells (LGAC)(p = 0.0026) from male NOD mice, a model of autoimmune dacryoadenitis in SS, relative to BALB/c controls. Primary mouse LGAC and human corneal epithelial cells (HCE-T cells) exposed to interferon-gamma, a cytokine elevated in SS, showed up to 9.6-fold (p ≤ 0.0001) and 25-fold (p ≤ 0.0001) increases in CX3CL1 gene expression, and 1.9-fold (p = 0.0005) and 196-fold (p ≤ 0.0001) increases in CX3CL1 protein expression, respectively. Moreover, exposure of HCE-T cells to recombinant human CTSS at activity equivalent to that in SS patient tears increased cellular CX3CL1 gene and protein expression by 2.8-fold (p = 0.0021) and 5.1-fold (p ≤ 0.0001), while increasing CX3CL1 in culture medium by 5.8-fold (p ≤ 0.0001). Flow cytometry demonstrated a 4.5-fold increase in CX3CR1-expressing immune cells (p ≤ 0.0001), including increased T-cells and macrophages, in LG from NOD mice relative to BALB/c. CTSS-mediated induction/cleavage of CX3CL1 may contribute to ocular surface and LG inflammation in SS. |
| 巻・号 | 10(1) |
| ページ | 1455 |
| 公開日 | 2020-1-29 |
| DOI | 10.1038/s41598-020-58337-4 |
| PII | 10.1038/s41598-020-58337-4 |
| PMID | 31996771 |
| PMC | PMC6989636 |
| MeSH | Animals Cathepsins / metabolism* Cells, Cultured Chemokine CX3CL1 / genetics Chemokine CX3CL1 / metabolism* Dacryocystitis Disease Models, Animal Epithelium, Corneal / metabolism* Humans Interferon-gamma / metabolism Lacrimal Apparatus / immunology* Male Mice Mice, Inbred BALB C Mice, Inbred NOD Sjogren's Syndrome / immunology* T-Lymphocytes / immunology* Tears / metabolism* Up-Regulation |
| IF | 3.998 |
| 引用数 | 0 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HCE-T(RCB2280) |