PMID- 27588757 OWN - NLM STAT- MEDLINE DCOM- 20170801 LR - 20220408 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 9 DP - 2016 TI - Platelet Supernatant Suppresses LPS-Induced Nitric Oxide Production from Macrophages Accompanied by Inhibition of NF-kappaB Signaling and Increased Arginase-1 Expression. PG - e0162208 LID - 10.1371/journal.pone.0162208 [doi] LID - e0162208 AB - We previously reported that mouse bone marrow-derived macrophages (BMDMs) that had been co-cultured with platelets exhibited lower susceptibility to bacterial lipopolysaccharide (LPS) and produced lower levels of nitric oxide (NO) and inflammatory cytokines including TNF-alpha and IL-6. The suppression of macrophage responses was mediated, at least in part, by platelet supernatant. In the present study, we assessed phenotypic changes of BMDMs induced by incubation with the supernatant from thrombin-activated platelets (PLT-sup) and found that BMDMs cultured with PLT-sup (PLT-BMDMs) expressed a lower level of inducible NO synthase (iNOS) and a higher level of arginase-1, both of which are involved in the L-arginine metabolism, upon stimulation with LPS or zymosan. We also examined possible modulation of the NF-kappaB signaling pathway and observed suppression of IkappaBalpha phosphorylation and a decrease of NF-kappaB p65 expression in LPS-stimulated PLT-BMDMs. These results suggest that PLT-sup suppresses inflammatory responses of BMDMs via negative regulation of NF-kappaB signaling leading to lowered expression of iNOS and enhanced L-arginine catabolism by arginase-1. FAU - Ando, Yusuke AU - Ando Y AD - Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan. FAU - Oku, Teruaki AU - Oku T AD - Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan. FAU - Tsuji, Tsutomu AU - Tsuji T AUID- ORCID: 0000-0001-7920-0336 AD - Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20160902 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 3.5.3.1 (Arg1 protein, mouse) RN - EC 3.5.3.1 (Arginase) SB - IM MH - Animals MH - Arginase/*metabolism MH - Blood Platelets/*metabolism MH - Coculture Techniques MH - Lipopolysaccharides/*pharmacology MH - Macrophages/*drug effects/metabolism MH - Mice MH - Mice, Inbred BALB C MH - NF-kappa B/*metabolism MH - Nitric Oxide/*metabolism MH - Signal Transduction/*drug effects PMC - PMC5010197 COIS- The authors have declared that no competing interests exist. EDAT- 2016/09/03 06:00 MHDA- 2017/08/02 06:00 PMCR- 2016/09/02 CRDT- 2016/09/03 06:00 PHST- 2016/05/19 00:00 [received] PHST- 2016/08/18 00:00 [accepted] PHST- 2016/09/03 06:00 [entrez] PHST- 2016/09/03 06:00 [pubmed] PHST- 2017/08/02 06:00 [medline] PHST- 2016/09/02 00:00 [pmc-release] AID - PONE-D-16-20239 [pii] AID - 10.1371/journal.pone.0162208 [doi] PST - epublish SO - PLoS One. 2016 Sep 2;11(9):e0162208. doi: 10.1371/journal.pone.0162208. eCollection 2016.