Human cardiac fibroblasts produce pro-inflammatory cytokines upon TLRs and RLRs stimulation

Abstract

Heart inflammation is one of the major causes of heart damage that leads to dilated cardiomyopathy and often progresses to end-stage heart failure. In the present study, we aimed to assess whether human cardiac cells could release immune mediators upon stimulation of Toll-like receptors (TLRs) and Retinoic acid-inducible gene (RIG)-I-like receptors (RLRs).Commercially available human cardiac fibroblasts and an immortalized human cardiomyocyte cell line were stimulated in vitro with TLR2, TLR3, and TLR4 agonists. In addition, cytosolic RLRs were activated in cardiac cells after transfection of polyinosinic-polycytidylic acid (PolyIC). Upon stimulation of TLR3, TLR4, MDA5, and RIG-I, but not upon stimulation of TLR2, human cardiac fibroblasts produced high amounts of the pro-inflammatory cytokines IL-6 and IL-8. On the contrary, the immortalized human cardiomyocyte cell line was unresponsive to the tested TLRs agonists. Upon RLRs stimulation, cardiac fibroblasts, and to a lesser extent the cardiomyocyte cell line, induced anti-viral IFN-β expression.These data demonstrate that human cardiac fibroblasts and an immortalized human cardiomyocyte cell line differently respond to various TLRs and RLRs ligands. In particular, human cardiac fibroblasts were able to induce pro-inflammatory and anti-viral cytokines on their own. These aspects will contribute to better understand the immunological function of the different cell populations that make up the cardiac tissue.

β-arrestin2 Mediates the Arginine Vasopressin-Induced Expression of IL-1β in Murine Hearts

“…Nevertheless, role of cardiac fibroblasts in promoting inflammation have attracted more attention recently. Cardiomyocytes [20], cardiac endothelial cells [21], cardiac fibroblasts [6,22,23], and cardiac infiltrates [24,25] were all reported to produce inflammatory cytokines that cause cardiac remodeling and dysfunction. Among them, IL-1β mainly comes from cardiac endothelial cells and cardiac fibroblasts and is strictly regulated by inflammasomes [26,27].…”

MAVS signaling is required for clearance of chikungunya heart infection and prevention of chronic inflammation in vascular tissue

“…We found that CHIKV-infected hearts display a significant yet transient production of proinflammatory chemokines and cytokines. Interestingly, it has been shown that upon TLRs or RIG-I-like receptor stimulation, human cardiac fibroblasts can produce proinflammatory cytokines and induce an antiviral immune response (Li et al, 2021). Therefore, the CHIKV-infected cardiac fibroblasts may be contributing to this transient production of immune modulators.…”

Co-interventions withClostridium butyricumand soluble dietary fiber targeting the gut microbiota improve MAFLDviathe Acly/Nrf2/NF-κB signaling pathway

“…Dietary saturated fatty acid induced NF-κB activation and nuclear translocation lead to the production of pro-inflammatory cytokines (IL-6, TNF-α and IL-1β). 31,32 The NF-κB signaling pathway is also a major contributor to MAFLD by mediating the activation of M1 macrophages. 33,34 Furthermore, stimulation of M1 macrophages with LPS activates NF-κB, which induces the expression of NOD-like receptor family 3 (NLRP3).…”