Abstract
Macrophage proinflammatory responses induced by oxidized low-density lipoproteins (oxLDL) contribute to atherosclerotic progression. Our previous data using mice lacking lipin-1 enzymatic activity in myeloid-derived cells demonstrated that stimulation of bone marrow-derived macrophages with oxLDL activates a lipin-1 dependent persistent PKCα/βII-ERK1/2-cJun signaling cascade that primes the macrophage to be hyper-responsive to subsequent proinflammatory stimulus. To further investigate the impact of lipin-1 enzymatic activity on oxLDL-induced macrophage proinflammatory responses, bone marrow-derived macrophages (BMDMs) were collected from mice lacking lipin-1 enzymatic activity in myeloid-derived cells and littermate control mice. Both the control BMDMs and BMDMs lacking lipin-1 enzymatic activity were then stimulated with oxLDL, lipopolysaccharide (LPS), or oxLDL and LPS. RNA was collected from the BMDMs and RNA sequencing was performed. The goal was to identify transcripts that are altered between the control BMDMs and BMDMs lacking lipin-1 enzymatic activity to define transcription factors and signaling pathways regulated by lipin-1 enzymatic activity on a global level. Our data demonstrates that the loss of lipin-1 enzymatic activity in BMDMs results in a reduction of proinflammatory transcripts, via loss of cJun activity, in response to the combination treatment of oxLDL and LPS when compared to the control BMDMs.
Published Version
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