Progranulin inhibits expression and release of chemokines CXCL9 and CXCL10 in a TNFR1 dependent manner
Progranulin (PGRN), a pleiotrophic growth factor, is known to play an important role in the maintenance and regulation of the homeostatic dynamics of normal tissue development, proliferation, regeneration, and host-defense. PGRN also has potent anti-inflammatory functionality, and deregulated PGRN is associated with rheumatoid arthritis and inflammatory bowel disease. We have previously reported that PGRN directly binds to TNFR and significantly enhances Treg population and stimulates IL-10 production. To further investigate PGRN's function in the immune system we performed a gene array analysis on CD4+ T cells from wild type B6 mice and PGRN -/- mice. We identified many chemokines and their receptors, among which CXCL9 and CXCL10 were most prominent, that were significantly induced in PGRN null mice. Administration of recombinant PGRN protein strongly inhibited TNF and IFN-γ-induced CXCL9 and CXCL10 expression. In addition, CXCL9 expression is strongly upregulated in PGRN KO mice and its level is correlated with severity of inflammation in a dermatitis model. Further, we have demonstrated that PGRN-mediated inhibition of chemokine expression largely depends on TNFR1. Taken together, this study provides new insights into the mechanisms underlying PGRN mediated regulation of various inflammatory and autoimmune diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Scientific reports - 6(2016) vom: 19. Feb., Seite 21115 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mundra, Jyoti Joshi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.12.2016 Date Revised 02.12.2018 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/srep21115 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM257623701 |
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| 100 | 1 | |a Mundra, Jyoti Joshi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Progranulin inhibits expression and release of chemokines CXCL9 and CXCL10 in a TNFR1 dependent manner |
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| 500 | |a Date Revised 02.12.2018 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Progranulin (PGRN), a pleiotrophic growth factor, is known to play an important role in the maintenance and regulation of the homeostatic dynamics of normal tissue development, proliferation, regeneration, and host-defense. PGRN also has potent anti-inflammatory functionality, and deregulated PGRN is associated with rheumatoid arthritis and inflammatory bowel disease. We have previously reported that PGRN directly binds to TNFR and significantly enhances Treg population and stimulates IL-10 production. To further investigate PGRN's function in the immune system we performed a gene array analysis on CD4+ T cells from wild type B6 mice and PGRN -/- mice. We identified many chemokines and their receptors, among which CXCL9 and CXCL10 were most prominent, that were significantly induced in PGRN null mice. Administration of recombinant PGRN protein strongly inhibited TNF and IFN-γ-induced CXCL9 and CXCL10 expression. In addition, CXCL9 expression is strongly upregulated in PGRN KO mice and its level is correlated with severity of inflammation in a dermatitis model. Further, we have demonstrated that PGRN-mediated inhibition of chemokine expression largely depends on TNFR1. Taken together, this study provides new insights into the mechanisms underlying PGRN mediated regulation of various inflammatory and autoimmune diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Chemokine CXCL10 |2 NLM | |
| 650 | 7 | |a Chemokine CXCL9 |2 NLM | |
| 650 | 7 | |a Intercellular Signaling Peptides and Proteins |2 NLM | |
| 650 | 7 | |a Progranulins |2 NLM | |
| 650 | 7 | |a Receptors, Tumor Necrosis Factor, Type I |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 700 | 1 | |a Jian, Jinlong |e verfasserin |4 aut | |
| 700 | 1 | |a Bhagat, Priyal |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Chuan-Ju |e verfasserin |4 aut | |
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