Interferon-β decreases LPS-induced neutrophil recruitment to cardiac fibroblasts
Introduction: Cardiac fibroblasts (CF) are crucial cells in damaged heart tissues, expressing TLR4, IFN-receptor and responding to lipopolysaccharide (LPS) and interferon-β (IFN-β) respectively. While CF interact with immune cells; however, their relationship with neutrophils remains understudied. A...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1122408/full |
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| author | Renatto Anfossi Renatto Anfossi Raúl Vivar Raúl Vivar Pedro Ayala Fabiola González-Herrera Claudio Espinoza-Pérez José Miguel Osorio Mauricio Román-Torres Samir Bolívar Guillermo Díaz-Araya Guillermo Díaz-Araya |
| author_facet | Renatto Anfossi Renatto Anfossi Raúl Vivar Raúl Vivar Pedro Ayala Fabiola González-Herrera Claudio Espinoza-Pérez José Miguel Osorio Mauricio Román-Torres Samir Bolívar Guillermo Díaz-Araya Guillermo Díaz-Araya |
| author_sort | Renatto Anfossi |
| collection | DOAJ |
| description | Introduction: Cardiac fibroblasts (CF) are crucial cells in damaged heart tissues, expressing TLR4, IFN-receptor and responding to lipopolysaccharide (LPS) and interferon-β (IFN-β) respectively. While CF interact with immune cells; however, their relationship with neutrophils remains understudied. Additionally, theimpact of LPS and IFN-β on CF-neutrophil interaction is poorly understood.Methods: Isolated CF from adult rats were treated with LPS, with or without IFN-β. This study examined IL-8 secretion, ICAM-1 and VCAM-1 expression, and neutrophil recruitment, as well as their effects on MMPs activity.Results: LPS triggered increased IL-8 expression and secretion, along with elevated ICAM-1 and VCAM-1 expression, all of which were blocked by TAK-242. Pre-treatment with IFN-β countered these LPS effects. LPS treated CF showed higher neutrophil recruitment (migration and adhesion) compared to unstimulated CF, an effect prevented by IFN-β. Ruxolitinib blocked these IFN-β anti-inflammatory effects, implicating JAK signaling. Analysis of culture medium zymograms from CF alone, and CF-neutrophils interaction, revealed that MMP2 was mainly originated from CF, while MMP9 could come from neutrophils. LPS and IFN-β boosted MMP2 secretion by CF. MMP9 activity in CF was low, and LPS or IFN-β had no significant impact. Pre-treating CF with LPS, IFN-β, or both before co-culture with neutrophils increased MMP2. Neutrophil co-culture increased MMP9 activity, with IFN-β pre-treatment reducing MMP9 compared to unstimulated CF.Conclusion: In CF, LPS induces the secretion of IL-8 favoring neutrophils recruitment and these effects were blocked by IFN-. The results highlight that CF-neutrophil interaction appears to influence the extracellular matrix through MMPs activity modulation. |
| first_indexed | 2024-03-11T23:16:09Z |
| format | Article |
| id | doaj.art-ff2d036fafee46b78b4f239e3e959d5a |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-11T23:16:09Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-ff2d036fafee46b78b4f239e3e959d5a2023-09-21T04:34:04ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-09-011110.3389/fcell.2023.11224081122408Interferon-β decreases LPS-induced neutrophil recruitment to cardiac fibroblastsRenatto Anfossi0Renatto Anfossi1Raúl Vivar2Raúl Vivar3Pedro Ayala4Fabiola González-Herrera5Claudio Espinoza-Pérez6José Miguel Osorio7Mauricio Román-Torres8Samir Bolívar9Guillermo Díaz-Araya10Guillermo Díaz-Araya11Unidad de Farmacia, Hospital Regional del Libertador Bernardo O’Higgins, Rancagua, ChileDepartamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, ChileDepartamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, ChileInstituto de Farmacología, Facultad de Medicina, Universidad de Chile, Santiago, ChileFacultad de Medicina, Pontifica Universidad Católica de Chile, Santiago de Chile, ChileInstituto de Farmacología, Facultad de Medicina, Universidad de Chile, Santiago, ChileDepartamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, ChileDepartamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, ChileDepartamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, ChileFacultad de Química y Farmacia, Universidad del Atlántico, Barranquilla, ColombiaDepartamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, ChileAdvanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, ChileIntroduction: Cardiac fibroblasts (CF) are crucial cells in damaged heart tissues, expressing TLR4, IFN-receptor and responding to lipopolysaccharide (LPS) and interferon-β (IFN-β) respectively. While CF interact with immune cells; however, their relationship with neutrophils remains understudied. Additionally, theimpact of LPS and IFN-β on CF-neutrophil interaction is poorly understood.Methods: Isolated CF from adult rats were treated with LPS, with or without IFN-β. This study examined IL-8 secretion, ICAM-1 and VCAM-1 expression, and neutrophil recruitment, as well as their effects on MMPs activity.Results: LPS triggered increased IL-8 expression and secretion, along with elevated ICAM-1 and VCAM-1 expression, all of which were blocked by TAK-242. Pre-treatment with IFN-β countered these LPS effects. LPS treated CF showed higher neutrophil recruitment (migration and adhesion) compared to unstimulated CF, an effect prevented by IFN-β. Ruxolitinib blocked these IFN-β anti-inflammatory effects, implicating JAK signaling. Analysis of culture medium zymograms from CF alone, and CF-neutrophils interaction, revealed that MMP2 was mainly originated from CF, while MMP9 could come from neutrophils. LPS and IFN-β boosted MMP2 secretion by CF. MMP9 activity in CF was low, and LPS or IFN-β had no significant impact. Pre-treating CF with LPS, IFN-β, or both before co-culture with neutrophils increased MMP2. Neutrophil co-culture increased MMP9 activity, with IFN-β pre-treatment reducing MMP9 compared to unstimulated CF.Conclusion: In CF, LPS induces the secretion of IL-8 favoring neutrophils recruitment and these effects were blocked by IFN-. The results highlight that CF-neutrophil interaction appears to influence the extracellular matrix through MMPs activity modulation.https://www.frontiersin.org/articles/10.3389/fcell.2023.1122408/fullInterleukin-8neutrophilscardiac fibroblastmetalloproteaseTLR4 |
| spellingShingle | Renatto Anfossi Renatto Anfossi Raúl Vivar Raúl Vivar Pedro Ayala Fabiola González-Herrera Claudio Espinoza-Pérez José Miguel Osorio Mauricio Román-Torres Samir Bolívar Guillermo Díaz-Araya Guillermo Díaz-Araya Interferon-β decreases LPS-induced neutrophil recruitment to cardiac fibroblasts Frontiers in Cell and Developmental Biology Interleukin-8 neutrophils cardiac fibroblast metalloprotease TLR4 |
| title | Interferon-β decreases LPS-induced neutrophil recruitment to cardiac fibroblasts |
| title_full | Interferon-β decreases LPS-induced neutrophil recruitment to cardiac fibroblasts |
| title_fullStr | Interferon-β decreases LPS-induced neutrophil recruitment to cardiac fibroblasts |
| title_full_unstemmed | Interferon-β decreases LPS-induced neutrophil recruitment to cardiac fibroblasts |
| title_short | Interferon-β decreases LPS-induced neutrophil recruitment to cardiac fibroblasts |
| title_sort | interferon β decreases lps induced neutrophil recruitment to cardiac fibroblasts |
| topic | Interleukin-8 neutrophils cardiac fibroblast metalloprotease TLR4 |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1122408/full |
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