PMID- 32407430 OWN - NLM STAT- MEDLINE DCOM- 20210408 LR - 20210408 IS - 2040-3372 (Electronic) IS - 2040-3364 (Linking) VI - 12 IP - 20 DP - 2020 May 28 TI - Pristine graphene induces innate immune training. PG - 11192-11200 LID - 10.1039/c9nr09661b [doi] AB - Graphene-based materials are of increasing interest for their potential use in biomedical applications. However, there is a need to gain a deeper understanding of how graphene modulates biological responses before moving towards clinical application. Innate immune training is a recently described phenomenon whereby cells of the innate immune system are capable of being programmed to generate an increased non-specific response upon subsequent challenge. This has been well established in the case of certain microbes and microbial products. However, little is known about the capacity of particulate materials, such as pristine graphene (pGr), to promote innate immune training. Here we report for the first time that while stimulation with pGr alone does not directly induce cytokine secretion by bone-marrow derived macrophages (BMDMs), it programs them for enhanced secretion of proinflammatory cytokines (IL-6, TNF-alpha) and a concomitant decrease in production of the regulatory cytokine, IL-10 after Toll-like receptor (TLR) ligand stimulation. This capacity of pGr to program cells for enhanced inflammatory responses could be overcome if the nanomaterial is incorporated in a collagen matrix. Our findings thus demonstrate the potential of graphene to modulate innate immunity over long timescales and have implications for the design and biomedical use of pGr-based materials. FAU - Lebre, Filipa AU - Lebre F AD - Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Ssciences Institute, Trinity College Dublin, Dublin 2, D02 PN40, Ireland. lavellee@tcd.ie. FAU - Boland, John B AU - Boland JB FAU - Gouveia, Pedro AU - Gouveia P FAU - Gorman, Aoife L AU - Gorman AL FAU - Lundahl, Mimmi L E AU - Lundahl MLE FAU - I Lynch, Roisin AU - I Lynch R FAU - O'Brien, Fergal J AU - O'Brien FJ FAU - Coleman, Jonathan AU - Coleman J FAU - Lavelle, Ed C AU - Lavelle EC LA - eng PT - Journal Article DEP - 20200514 PL - England TA - Nanoscale JT - Nanoscale JID - 101525249 RN - 0 (Fullerenes) RN - 0 (Monokines) RN - 0 (Toll-Like Receptors) RN - 0 (pristine (C60)) SB - IM MH - Animals MH - Fullerenes/chemistry/*pharmacology MH - Immunity, Innate/*drug effects MH - Macrophages/cytology/*immunology MH - Mice MH - Monokines/*immunology MH - Toll-Like Receptors/*immunology EDAT- 2020/05/15 06:00 MHDA- 2021/04/10 06:00 CRDT- 2020/05/15 06:00 PHST- 2020/05/15 06:00 [pubmed] PHST- 2021/04/10 06:00 [medline] PHST- 2020/05/15 06:00 [entrez] AID - 10.1039/c9nr09661b [doi] PST - ppublish SO - Nanoscale. 2020 May 28;12(20):11192-11200. doi: 10.1039/c9nr09661b. Epub 2020 May 14.