Introduction: Cardiac Fibroblasts (CFs) play a key role in the homeostatic maintenance of ECM and healing after cardiac injury. After tissue injury, they are differentiated to cardiac myofibroblast (CMFs) which are characterized by increased collagens synthesis and alpha-smooth muscle actin expression and assembly, a contractile protein and CMFs marker. In addition, CFs express TLR4 receptor and play an active role on inflammatory response after tissue injury. On CFs lipopolysaccharide (LPS), activates TLR4 and induces MCP-1 and IL-8 secretion, triggering monocytes and neutrophils migration. In addition, LPS increases ICAM-1 and VCAM-1 expression levels, and consequently, increases leukocytes adhesion on CF. Resolvin D1and E1 (RvD1- RvE1) two novel specialized proresolvin mediators, decreases the inflammatory response, promoting the cessation of leukocyte recruitment; however, it is unknown whether RvD1 - RvE1 regulates the inflammatory response triggered by LPS on CF and if it consequently decreases leukocytes recruitment.
Objective: To demonstrate that in CF RvD1 - RvE1 decreases MCP-1, ICAM-1 and VCAM-1 expression levels, and consequently leukocytes recruitment LPS-induced.
Materials and methods: neonate rat CF were serum starved for 24 h, then stimulated with LPS by other 24 h in presence or absence of RvD1 or RvE1. RvD1 and RvE1 effects on CF viability and proliferation was evaluated by AlamarBlue, ALX, ChemR23, ICAM-1, VCAM-1 were determined by immunowestern blot. The adhesion of leukocytes to FC was analyzed by microscopy.
Results: CF express both resolvin receptors ALX (for RvD1) and ChemR23 (for RvE1). RvD1 or RvE1 in a time and concentration dependent manner did not show effect on CF viability and proliferation. Also RvD1or RvE1 by themselves did not affect ICAM-1 and VCAM-1 expression levels; and also MCP-1 secretion However, RvD1 and RvE1 decreased MCP-1 secretion, ICAM-1 and VCAM-1 expression levels LPS-induced. Finally, RvD1 and RvE1 decreased leukocyte adhesion LPS-induced on CF.
Conclusion: Our results suggest that CF express both resolvin receptors, and that in LPS-stimulated CF, RvD1 and RvE1 show an anti-inflammatory effect reducing MCP-1 secretion; preventing the increases on ICAM-1 and VCAM-1 expression levels; and consequently, reducing leukocyte recruitment by CF.
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