PMID- 36971014 OWN - NLM STAT- MEDLINE DCOM- 20231020 LR - 20231020 IS - 1873-3468 (Electronic) IS - 0014-5793 (Linking) VI - 597 IP - 9 DP - 2023 May TI - MyD88 and not TRIF knockout is sufficient to abolish LPS-induced inflammatory responses in bone-derived macrophages. PG - 1225-1232 LID - 10.1002/1873-3468.14616 [doi] AB - Macrophages play an important role in the response to infection and/or repair of injury in tissues. To examine the NF-kappaB pathway in response to an inflammatory stimulus, we used wild-type bone-marrow-derived macrophages (BMDMs) or BMDMs with knockout (KO) of myeloid differentiation primary response 88 (MyD88) and/or Toll/interleukin-1 receptor domain-containing adapter-inducing interferon-beta (TRIF) via CRISPR/Cas9. Following treatment of BMDMs with lipopolysaccharide (LPS) to induce an inflammatory response, translational signalling of NF-kappaB was quantified via immunoblot and cytokines were measured. Our findings reveal that MyD88 KO, but not TRIF KO, decreased LPS-induced NF-kappaB signalling, and 10% expression of basal MyD88 expression was sufficient to partially rescue the abolished inflammatory cytokine secretion observed upon MyD88 KO. CI - (c) 2023 Federation of European Biochemical Societies. FAU - Reynoso, Marinaliz AU - Reynoso M AD - U.S. Army Research Institute of Environmental Medicine, Natick, MA, USA. FAU - Hobbs, Stuart AU - Hobbs S AD - U.S. Army Research Institute of Environmental Medicine, Natick, MA, USA. FAU - Kolb, Alexander L AU - Kolb AL AD - U.S. Army Research Institute of Environmental Medicine, Natick, MA, USA. FAU - Matheny, Ronald W Jr AU - Matheny RW Jr AD - Military Operational Medicine Research Program, Fort Detrick, MA, USA. FAU - Roberts, Brandon M AU - Roberts BM AUID- ORCID: 0000-0003-0395-6967 AD - U.S. Army Research Institute of Environmental Medicine, Natick, MA, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230404 PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Adaptor Proteins, Vesicular Transport) RN - 0 (Lipopolysaccharides) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B) RN - 0 (Toll-Like Receptor 4) SB - IM MH - Adaptor Proteins, Signal Transducing/metabolism MH - Adaptor Proteins, Vesicular Transport/genetics/metabolism MH - *Lipopolysaccharides/toxicity/metabolism MH - Macrophages/metabolism MH - Myeloid Differentiation Factor 88/genetics/metabolism MH - *NF-kappa B/genetics/metabolism MH - Toll-Like Receptor 4/genetics/metabolism MH - Animals MH - Mice OTO - NOTNLM OT - CRISPR/Cas9 OT - TLR4 OT - bonemarrow-derived macrophages OT - inflammation OT - interleukin-10 OT - tumour necrosis factor EDAT- 2023/03/28 06:00 MHDA- 2023/05/10 06:42 CRDT- 2023/03/27 05:14 PHST- 2023/02/24 00:00 [revised] PHST- 2023/01/20 00:00 [received] PHST- 2023/02/28 00:00 [accepted] PHST- 2023/05/10 06:42 [medline] PHST- 2023/03/28 06:00 [pubmed] PHST- 2023/03/27 05:14 [entrez] AID - 10.1002/1873-3468.14616 [doi] PST - ppublish SO - FEBS Lett. 2023 May;597(9):1225-1232. doi: 10.1002/1873-3468.14616. Epub 2023 Apr 4.