Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration [IMMUNE REGULATION]
Parmar, T., Parmar, V. M., Perusek, L., Georges, A., Takahashi, M., Crabb, J. W., Maeda, A.
The American Association of Immunologists (AAI)
Published 2018
The American Association of Immunologists (AAI)
Published 2018
| Publication Date: |
2018-04-24
|
|---|---|
| Publisher: |
The American Association of Immunologists (AAI)
|
| Print ISSN: |
0022-1767
|
| Electronic ISSN: |
1550-6606
|
| Topics: |
Medicine
|
| Published by: |
| _version_ | 1836398906889469954 |
|---|---|
| autor | Parmar, T., Parmar, V. M., Perusek, L., Georges, A., Takahashi, M., Crabb, J. W., Maeda, A. |
| beschreibung | It has become increasingly important to understand how retinal inflammation is regulated because inflammation plays a role in retinal degenerative diseases. Lipocalin 2 (LCN2), an acute stress response protein with multiple innate immune functions, is increased in ATP-binding cassette subfamily A member 4 ( Abca4 ) –/– retinol dehydrogenase 8 ( Rdh8 ) –/– double-knockout mice, an animal model for Stargardt disease and age-related macular degeneration (AMD). To examine roles of LCN2 in retinal inflammation and degeneration, Lcn2 –/– Abca4 –/– Rdh8 –/– triple-knockout mice were generated. Exacerbated inflammation following light exposure was observed in Lcn2 –/– Abca4 –/– Rdh8 –/– mice as compared with Abca4 –/– Rdh8 –/– mice, with upregulation of proinflammatory genes and microglial activation. RNA array analyses revealed an increase in immune response molecules such as Ccl8 , Ccl2 , and Cxcl10 . To further probe a possible regulatory role for LCN2 in retinal inflammation, we examined the in vitro effects of LCN2 on NF-B signaling in human retinal pigmented epithelial (RPE) cells differentiated from induced pluripotent stem cells derived from healthy donors. We found that LCN2 induced expression of antioxidant enzymes heme oxygenase 1 and superoxide dismutase 2 in these RPE cells and could inhibit the cytotoxic effects of H 2 O 2 and LPS. ELISA revealed increased LCN2 levels in plasma of patients with Stargardt disease, retinitis pigmentosa, and age-related macular degeneration as compared with healthy controls. Finally, overexpression of LCN2 in RPE cells displayed protection from cell death. Overall these results suggest that LCN2 is involved in prosurvival responses during cell stress and plays an important role in regulating inflammation during retinal degeneration. |
| citation_standardnr | 6242843 |
| datenlieferant | ipn_articles |
| feed_id | 333 |
| feed_publisher | The American Association of Immunologists (AAI) |
| feed_publisher_url | http://www.aai.org/ |
| insertion_date | 2018-04-24 |
| journaleissn | 1550-6606 |
| journalissn | 0022-1767 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The American Association of Immunologists (AAI) |
| quelle | Journal of Immunology |
| relation | http://www.jimmunol.org/cgi/content/short/200/9/3128?rss=1 |
| search_space | articles |
| shingle_author_1 | Parmar, T., Parmar, V. M., Perusek, L., Georges, A., Takahashi, M., Crabb, J. W., Maeda, A. |
| shingle_author_2 | Parmar, T., Parmar, V. M., Perusek, L., Georges, A., Takahashi, M., Crabb, J. W., Maeda, A. |
| shingle_author_3 | Parmar, T., Parmar, V. M., Perusek, L., Georges, A., Takahashi, M., Crabb, J. W., Maeda, A. |
| shingle_author_4 | Parmar, T., Parmar, V. M., Perusek, L., Georges, A., Takahashi, M., Crabb, J. W., Maeda, A. |
| shingle_catch_all_1 | Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration [IMMUNE REGULATION] It has become increasingly important to understand how retinal inflammation is regulated because inflammation plays a role in retinal degenerative diseases. Lipocalin 2 (LCN2), an acute stress response protein with multiple innate immune functions, is increased in ATP-binding cassette subfamily A member 4 ( Abca4 ) –/– retinol dehydrogenase 8 ( Rdh8 ) –/– double-knockout mice, an animal model for Stargardt disease and age-related macular degeneration (AMD). To examine roles of LCN2 in retinal inflammation and degeneration, Lcn2 –/– Abca4 –/– Rdh8 –/– triple-knockout mice were generated. Exacerbated inflammation following light exposure was observed in Lcn2 –/– Abca4 –/– Rdh8 –/– mice as compared with Abca4 –/– Rdh8 –/– mice, with upregulation of proinflammatory genes and microglial activation. RNA array analyses revealed an increase in immune response molecules such as Ccl8 , Ccl2 , and Cxcl10 . To further probe a possible regulatory role for LCN2 in retinal inflammation, we examined the in vitro effects of LCN2 on NF-B signaling in human retinal pigmented epithelial (RPE) cells differentiated from induced pluripotent stem cells derived from healthy donors. We found that LCN2 induced expression of antioxidant enzymes heme oxygenase 1 and superoxide dismutase 2 in these RPE cells and could inhibit the cytotoxic effects of H 2 O 2 and LPS. ELISA revealed increased LCN2 levels in plasma of patients with Stargardt disease, retinitis pigmentosa, and age-related macular degeneration as compared with healthy controls. Finally, overexpression of LCN2 in RPE cells displayed protection from cell death. Overall these results suggest that LCN2 is involved in prosurvival responses during cell stress and plays an important role in regulating inflammation during retinal degeneration. Parmar, T., Parmar, V. M., Perusek, L., Georges, A., Takahashi, M., Crabb, J. W., Maeda, A. The American Association of Immunologists (AAI) 0022-1767 00221767 1550-6606 15506606 |
| shingle_catch_all_2 | Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration [IMMUNE REGULATION] It has become increasingly important to understand how retinal inflammation is regulated because inflammation plays a role in retinal degenerative diseases. Lipocalin 2 (LCN2), an acute stress response protein with multiple innate immune functions, is increased in ATP-binding cassette subfamily A member 4 ( Abca4 ) –/– retinol dehydrogenase 8 ( Rdh8 ) –/– double-knockout mice, an animal model for Stargardt disease and age-related macular degeneration (AMD). To examine roles of LCN2 in retinal inflammation and degeneration, Lcn2 –/– Abca4 –/– Rdh8 –/– triple-knockout mice were generated. Exacerbated inflammation following light exposure was observed in Lcn2 –/– Abca4 –/– Rdh8 –/– mice as compared with Abca4 –/– Rdh8 –/– mice, with upregulation of proinflammatory genes and microglial activation. RNA array analyses revealed an increase in immune response molecules such as Ccl8 , Ccl2 , and Cxcl10 . To further probe a possible regulatory role for LCN2 in retinal inflammation, we examined the in vitro effects of LCN2 on NF-B signaling in human retinal pigmented epithelial (RPE) cells differentiated from induced pluripotent stem cells derived from healthy donors. We found that LCN2 induced expression of antioxidant enzymes heme oxygenase 1 and superoxide dismutase 2 in these RPE cells and could inhibit the cytotoxic effects of H 2 O 2 and LPS. ELISA revealed increased LCN2 levels in plasma of patients with Stargardt disease, retinitis pigmentosa, and age-related macular degeneration as compared with healthy controls. Finally, overexpression of LCN2 in RPE cells displayed protection from cell death. Overall these results suggest that LCN2 is involved in prosurvival responses during cell stress and plays an important role in regulating inflammation during retinal degeneration. Parmar, T., Parmar, V. M., Perusek, L., Georges, A., Takahashi, M., Crabb, J. W., Maeda, A. The American Association of Immunologists (AAI) 0022-1767 00221767 1550-6606 15506606 |
| shingle_catch_all_3 | Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration [IMMUNE REGULATION] It has become increasingly important to understand how retinal inflammation is regulated because inflammation plays a role in retinal degenerative diseases. Lipocalin 2 (LCN2), an acute stress response protein with multiple innate immune functions, is increased in ATP-binding cassette subfamily A member 4 ( Abca4 ) –/– retinol dehydrogenase 8 ( Rdh8 ) –/– double-knockout mice, an animal model for Stargardt disease and age-related macular degeneration (AMD). To examine roles of LCN2 in retinal inflammation and degeneration, Lcn2 –/– Abca4 –/– Rdh8 –/– triple-knockout mice were generated. Exacerbated inflammation following light exposure was observed in Lcn2 –/– Abca4 –/– Rdh8 –/– mice as compared with Abca4 –/– Rdh8 –/– mice, with upregulation of proinflammatory genes and microglial activation. RNA array analyses revealed an increase in immune response molecules such as Ccl8 , Ccl2 , and Cxcl10 . To further probe a possible regulatory role for LCN2 in retinal inflammation, we examined the in vitro effects of LCN2 on NF-B signaling in human retinal pigmented epithelial (RPE) cells differentiated from induced pluripotent stem cells derived from healthy donors. We found that LCN2 induced expression of antioxidant enzymes heme oxygenase 1 and superoxide dismutase 2 in these RPE cells and could inhibit the cytotoxic effects of H 2 O 2 and LPS. ELISA revealed increased LCN2 levels in plasma of patients with Stargardt disease, retinitis pigmentosa, and age-related macular degeneration as compared with healthy controls. Finally, overexpression of LCN2 in RPE cells displayed protection from cell death. Overall these results suggest that LCN2 is involved in prosurvival responses during cell stress and plays an important role in regulating inflammation during retinal degeneration. Parmar, T., Parmar, V. M., Perusek, L., Georges, A., Takahashi, M., Crabb, J. W., Maeda, A. The American Association of Immunologists (AAI) 0022-1767 00221767 1550-6606 15506606 |
| shingle_catch_all_4 | Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration [IMMUNE REGULATION] It has become increasingly important to understand how retinal inflammation is regulated because inflammation plays a role in retinal degenerative diseases. Lipocalin 2 (LCN2), an acute stress response protein with multiple innate immune functions, is increased in ATP-binding cassette subfamily A member 4 ( Abca4 ) –/– retinol dehydrogenase 8 ( Rdh8 ) –/– double-knockout mice, an animal model for Stargardt disease and age-related macular degeneration (AMD). To examine roles of LCN2 in retinal inflammation and degeneration, Lcn2 –/– Abca4 –/– Rdh8 –/– triple-knockout mice were generated. Exacerbated inflammation following light exposure was observed in Lcn2 –/– Abca4 –/– Rdh8 –/– mice as compared with Abca4 –/– Rdh8 –/– mice, with upregulation of proinflammatory genes and microglial activation. RNA array analyses revealed an increase in immune response molecules such as Ccl8 , Ccl2 , and Cxcl10 . To further probe a possible regulatory role for LCN2 in retinal inflammation, we examined the in vitro effects of LCN2 on NF-B signaling in human retinal pigmented epithelial (RPE) cells differentiated from induced pluripotent stem cells derived from healthy donors. We found that LCN2 induced expression of antioxidant enzymes heme oxygenase 1 and superoxide dismutase 2 in these RPE cells and could inhibit the cytotoxic effects of H 2 O 2 and LPS. ELISA revealed increased LCN2 levels in plasma of patients with Stargardt disease, retinitis pigmentosa, and age-related macular degeneration as compared with healthy controls. Finally, overexpression of LCN2 in RPE cells displayed protection from cell death. Overall these results suggest that LCN2 is involved in prosurvival responses during cell stress and plays an important role in regulating inflammation during retinal degeneration. Parmar, T., Parmar, V. M., Perusek, L., Georges, A., Takahashi, M., Crabb, J. W., Maeda, A. The American Association of Immunologists (AAI) 0022-1767 00221767 1550-6606 15506606 |
| shingle_title_1 | Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration [IMMUNE REGULATION] |
| shingle_title_2 | Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration [IMMUNE REGULATION] |
| shingle_title_3 | Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration [IMMUNE REGULATION] |
| shingle_title_4 | Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration [IMMUNE REGULATION] |
| timestamp | 2025-06-30T23:34:30.739Z |
| titel | Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration [IMMUNE REGULATION] |
| titel_suche | Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration [IMMUNE REGULATION] |
| topic | WW-YZ |
| uid | ipn_articles_6242843 |