biostudies-literatureUnknownArp NLNIAID NIH HHSNHLBI NIH HHSNCI NIH HHSNIGMS NIH HHSNitric oxide (NO•) is an important signaling molecule in many biological processes, including immune response. During response to classical activation stimuli lipopolysaccharide (LPS) and interferon-γ (IFNγ), macrophages generate NO• via inducible nitric oxide synthase (iNOS). To comprehensively define the effects of NO•, we applied a multi-omic strategy integrating proteomics and transcriptomics to profile murine macrophages across conditions with or without LPS/IFNγ-activation, with or without iNOS expression or exogenous NO• donor treatment. The results revealed NO• has broad, yet selected and controlled, regulatory effects, playing a key role in coordinating the systematic remodeling during macrophage classical activation. Among the proteins that are most suppressed in a NO•-dependent bioRxiv : the preprint server for biology2025.12.31.697202https://www.ebi.ac.uk/biostudies/studies/S-EPMC12776429biostudies-literatureMulti-omic analysis reveals nitric oxide dependent remodeling in classically activated macrophages and identifies negative regulation mediated by AKR1A1.PMC12776429R35 GM147014T32 GM140935F30 AI183563T32 GM135066P41 GM108538R35 GM118027F30 HL174128P30 CA014520Votava JAHuttenlocher AUrquiza USMorgenstern MFan JArp NLJohn SVStevens JJSchrope JHCoon JJfalseMulti-omic analysis reveals nitric oxide dependent remodeling in classically activated macrophages and identifies negative regulation mediated by AKR1A1.Nitric oxide (NO•) is an important signaling molecule in many biological processes, including immune response. During response to classical activation stimuli lipopolysaccharide (LPS) and interferon-γ (IFNγ), macrophages generate NO• via inducible nitric oxide synthase (iNOS). To comprehensively define the effects of NO•, we applied a multi-omic strategy integrating proteomics and transcriptomics to profile murine macrophages across conditions with or without LPS/IFNγ-activation, with or without iNOS expression or exogenous NO• donor treatment. The results revealed NO• has broad, yet selected and controlled, regulatory effects, playing a key role in coordinating the systematic remodeling during macrophage classical activation. Among the proteins that are most suppressed in a NO•-dependent 2026-01-01T00:00:00Z2026 Jan2026-06-12T03:14:58.063Z2026-06-12T03:08:14.619ZS-EPMC127764294150923910.64898/2025.12.31.697202