PMID- 33049560 OWN - NLM STAT- MEDLINE DCOM- 20210125 LR - 20210125 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 128 DP - 2020 Dec TI - Helminth-derived peptide GK-1 induces Myd88-dependent pro-inflammatory signaling events in bone marrow-derived antigen-presenting cells. PG - 22-32 LID - S0161-5890(20)30491-0 [pii] LID - 10.1016/j.molimm.2020.09.015 [doi] AB - GK-1 is an immunomodulatory, 18-aa-long peptide that has been proved to promote the activation of mouse peritoneal macrophages and LPS-pulsed mouse bone marrow-derived dendritic cells (BM-DCs). This study is aimed to explore the mechanisms underlying the activation of these antigen-presenting cells (APCs) by GK-1. In our study, GK-1 up-regulated in vitro the expression of CD86 and CD40, and it increased the secretion of NO in bone marrow-derived macrophages (BMDMs). In BM-DCs, GK-1 upregulated the expression of MHC class II and CD86. Additionally, GK-1 was found to be involved in the phosphorylation of MAPK p38, JNK and ERK 1/2 and in Myd88-dependent activation of NF-kappaB in both antigen-presenting cell types. In vivo, GK-1 increased the secretion of IL-15, CCL2, and IL-6 through a Myd88-dependent mechanism. This study demonstrated that GK-1 promotes the activation and effector activity of APCs through a mechanism dependent on Myd88, probably involving a Toll-like receptor as a target. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Montero, Laura AU - Montero L AD - Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, 04510, Mexico. Electronic address: lau_mlcrl@yahoo.com. FAU - Cervantes-Torres, Jacquelynne AU - Cervantes-Torres J AD - Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, 04510, Mexico. Electronic address: jcervantes@iibiomedicas.unam.mx. FAU - Sciutto, Edda AU - Sciutto E AD - Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, 04510, Mexico. Electronic address: edda@unam.mx. FAU - Fragoso, Gladis AU - Fragoso G AD - Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, 04510, Mexico. Electronic address: gladis@unam.mx. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201010 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (B7-2 Antigen) RN - 0 (CD40 Antigens) RN - 0 (Cytokines) RN - 0 (Helminth Proteins) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Peptides, Cyclic) RN - 0 (cyclo(cysteinyl-glycyl-aspargyl-seryl-aspargyl-prolyl-lysyl-seryl-cysteine)) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Antigen-Presenting Cells/*metabolism MH - B7-2 Antigen/metabolism MH - Bone Marrow/*metabolism MH - Bone Marrow Cells/metabolism MH - CD40 Antigens/metabolism MH - Cells, Cultured MH - Cytokines MH - Dendritic Cells/metabolism MH - Female MH - Helminth Proteins/*metabolism MH - Helminths/*metabolism MH - Inflammation/*metabolism MH - Macrophages, Peritoneal/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinases/metabolism MH - Myeloid Differentiation Factor 88/*metabolism MH - Peptides, Cyclic/*metabolism MH - Phosphorylation/physiology MH - Signal Transduction/physiology OTO - NOTNLM OT - Dendritic cells OT - GK-1 peptide OT - MAPKs OT - Macrophages OT - NF-kappaB EDAT- 2020/10/14 06:00 MHDA- 2021/01/26 06:00 CRDT- 2020/10/13 20:14 PHST- 2020/02/18 00:00 [received] PHST- 2020/09/19 00:00 [revised] PHST- 2020/09/21 00:00 [accepted] PHST- 2020/10/14 06:00 [pubmed] PHST- 2021/01/26 06:00 [medline] PHST- 2020/10/13 20:14 [entrez] AID - S0161-5890(20)30491-0 [pii] AID - 10.1016/j.molimm.2020.09.015 [doi] PST - ppublish SO - Mol Immunol. 2020 Dec;128:22-32. doi: 10.1016/j.molimm.2020.09.015. Epub 2020 Oct 10.