Cardiac fibroblast cytokine profiles induced by proinflammatory or profibrotic stimuli promote monocyte recruitment and modulate macrophage M1/M2 balance in vitro

Humeres, Claudio; Vivar, Raúl; Boza, Pía; Muñoz, Claudia; Bolívar, Samir; Anfossi, Renatto; Osorio, José Miguel; Olivares-Silva, Francisco; Garcı́a, Lorena; Díaz‐Araya, Guillermo

doi:10.1016/j.yjmcc.2016.10.014

Cited by 51 publications

(44 citation statements)

References 57 publications

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“…As opposed to moDCs, fibroblasts secretions appeared to prevent early steps of monocytes differentiation and pro‐inflammatory profile in our study. Although fibroblasts are typically described as contributing to monocytes chemotaxis, recent macrophages studies have reported anti‐inflammatory activities for fibroblasts on monocytes/macrophages . Collectively, these data and our study highlight an interesting role for fibroblasts in fine tuning the pro‐ and anti‐inflammatory balance.…”

Section: Discussionsupporting

confidence: 72%

Tissue microenvironment initiates an immune response to structural components of Staphylococcus aureus

Mainzer

Packard

Bordes

et al. 2019

Experimental Dermatology

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Cell-to-cell communication in skin participates to the maintenance of homeostatic responses to foreign substances. Certain strains of Staphylococcus (S) aureus are vicious pathogens that cause deleterious effects in host cells and tissues. Both secreted toxins and structural components of S. aureus trigger an immune response, though how S. aureus stimulates host immune responses is poorly understood. We explored here how keratinocytes and fibroblasts initiate the first steps of an immune response by activating dendritic cells (DCs) through recognition of structural components of S. aureus. We treated monocyte-derived Langerhans cells (moLCs) and monocyte-derived DCs (moDCs) with conditioned media from keratinocytes (K-CM) and fibroblasts (F-CM) treated with heat-killed S. aureus (HKSA) respectively, or directly with HKSA. Immune and inflammatory responses from keratinocytes, fibroblasts, moLCs and moDCs were assessed by analysis of cell surface markers and cytokine production using flow cytometry, real-time PCR and ELISA assays. K-CM and F-CM increased the expression of CD86 and HLA-DR on moLCs and moDCs, in association with a specific cytokine profile. K-CM upregulated TNFA, IL-1B and GM-CSF mRNA expression in moLCs, while F-CM upregulated IL-12 and downregulated TNFA and TGFB mRNA expression in moDCs. Additionally, F-CM attenuated the induction of an inflammatory profile in monocytes. The recognition of structural components from S. aureus by cutaneous microenvironment induces the activation and the expression of specific cytokines from LCs and DCs.

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Section: Discussionsupporting

confidence: 72%

Tissue microenvironment initiates an immune response to structural components of Staphylococcus aureus

Mainzer

Packard

Bordes

et al. 2019

Experimental Dermatology

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“…27 Conversely, MCP-1 knockout produced inefficient cardiac remodelling, characterized by a prolonged inflammatory phase and a delay in the formation of granulation tissue and wound healing. 27 Our study indicates Figure 5). Inversely, FSP knockdown generated underexpression of these inflammatory cytokines and signalling molecules ( Figure 5).…”

Section: Similarmentioning

confidence: 99%

FSP1 promotes the biofunctions of adventitial fibroblast through the crosstalk among RAGE, JAK2/STAT3 and Wnt3a/β‐catenin signalling pathways

Liu

et al. 2019

J Cellular Molecular Medi

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Emerging evidence indicates that fibroblast‐specific protein 1 (FSP1) provides vital effects in cell biofunctions. However, whether FSP1 influences the adventitial fibroblast (AF) and vascular remodelling remains unclear. Therefore, we investigated the potential role and action mechanism of FSP1‐mediated AF bioactivity. AFs were cultured and stimulated with FSP1 and siRNA‐FSP1 in vitro. Viability assays demonstrated that siRNA‐FSP1 counteracted AFs proliferative, migratory and adherent abilities enhanced with FSP1. Flow cytometry revealed that FSP1 increased AFs number in S phase and decreased cellular apoptosis. Contrarily, siRNA‐FSP1 displayed the contrary results. RT‐PCR, Western blotting and immunocytochemistry showed that FSP1 synchronously up‐regulated the expression of molecules in RAGE, JAK2/STAT3 and Wnt3a/β‐catenin pathways and induced a proinflammatory cytokine profile characterized by high levels of MCP‐1, ICAM‐1 and VCAM‐1. Conversely, FSP1 knockdown reduced the expression of these molecules and cytokines. The increased number of autophagosomes in FSP1‐stimulated group and fewer autophagic corpuscles in siRNA‐FSP1 group was observed by transmission electron microscope (TEM). Autophagy‐related proteins (LC3B, beclin‐1 and Apg7) were higher in FSP1 group than those in other groups. Conversely, the expression of p62 protein was shown an opposite trend of variation. Therefore, these pathways can promote AFs bioactivity, facilitate autophagy and induce the expression of the proinflammatory cytokines. Contrarily, siRNA‐FSP1 intercepts the crosstalk of these pathways, suppresses AF functions, restrains autophagy and attenuates the expression of the inflammatory factors. Our findings indicate that crosstalk among RAGE, STAT3/JAK2 and Wnt3a/β‐catenin signalling pathways may account for the mechanism of AF functions with the stimulation of FSP1.

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“…Couture et al (2009), have shown that TNF-α and PMA increase neutrophil recruitment by CF. Previous results from our laboratory have shown that in CF, TLR4 activation by LPS, induces monocyte recruitment by CF themselves, due initially to the monocyte migration favored by MCP-1 secretion; whereas ICAM-1 and VCAM-1 expression in turn favors monocyte adhesion (Humeres et al, 2016). Our results show that in CF, IFN-β activates STAT3 to inhibit LPS-induced ICAM-1 and VCAM-1 expression.…”

Section: Discussionmentioning

confidence: 90%

“…Cardiac fibroblast were isolated from adult Sprague Dawley Rats (3–4 weeks old) using enzymatic digestion, as previously described (Humeres et al, 2016). Briefly, rats were anesthetized by ketamine/xylazine injection and their hearts extracted in an aseptic environment.…”

Section: Methodsmentioning

confidence: 99%

IFN-β Plays Both Pro- and Anti-inflammatory Roles in the Rat Cardiac Fibroblast Through Differential STAT Protein Activation

et al. 2018

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Cardiac fibroblasts (CFs) contribute to theinflammatory response to tissue damage, secreting both pro- and anti-inflammatory cytokines and chemokines. Interferon beta (IFN-β) induces the phosphorylation of signal transducer and activator of transcription (STAT) proteins through the activation of its own receptor, modulating the secretion of cytokines and chemokines which regulate inflammation. However, the role of IFN-β and STAT proteins in modulating the inflammatory response of CF remains unknown. CF were isolated from adult male rats and subsequently stimulated with IFN-β to evaluate the participation of STAT proteins in secreting chemokines, cytokines, cell adhesion proteins expression and in their capacity to recruit neutrophils. In addition, in CF in which the TRL4 receptor was pre-activated, the effect of INF-β on the aforementioned responses was also evaluated. Cardiac fibroblasts stimulation with IFN-β showed an increase in STAT1, STAT2, and STAT3 phosphorylation. IFN-β stimulation through STAT1 activation increased proinflammatory chemokines MCP-1 and IP-10 secretion, whereas IFN-β induced activation of STAT3 increased cytokine secretion of anti-inflammatory IL-10. Moreover, in TLR4-activated CF, IFN-β through STAT2 and/or STAT3, produced an anti-inflammatory effect, reducing pro-IL-1β, TNF-α, IL-6, MCP-1, and IP-10 secretion; and decreasing neutrophil recruitment by decreasing ICAM-1 and VCAM-1 expression. Altogether, our results indicate that IFN-β exerts both pro-inflammatory and anti-inflammatory effects in non-stimulated CF, through differential activation of STAT proteins. When CF were previously treated with an inflammatory agent such as TLR-4 activation, IFN-β effects were predominantly anti-inflammatory.

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Cardiac fibroblast cytokine profiles induced by proinflammatory or profibrotic stimuli promote monocyte recruitment and modulate macrophage M1/M2 balance in vitro

Cited by 51 publications

References 57 publications

Tissue microenvironment initiates an immune response to structural components of Staphylococcus aureus

Tissue microenvironment initiates an immune response to structural components of Staphylococcus aureus

FSP1 promotes the biofunctions of adventitial fibroblast through the crosstalk among RAGE, JAK2/STAT3 and Wnt3a/β‐catenin signalling pathways

IFN-β Plays Both Pro- and Anti-inflammatory Roles in the Rat Cardiac Fibroblast Through Differential STAT Protein Activation

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