PMID- 33638611 OWN - NLM STAT- MEDLINE DCOM- 20220223 LR - 20220223 IS - 1552-4965 (Electronic) IS - 1549-3296 (Linking) VI - 109 IP - 9 DP - 2021 Sep TI - 10-hydroxy-2-decenoic acid a bio-immunomodulator in tissue engineering; generates tolerogenic dendritic cells by blocking the toll-like receptor4. PG - 1575-1587 LID - 10.1002/jbm.a.37152 [doi] AB - Dendritic cells (DCs), in response to the biomaterials, utilize toll-like receptors (TLRs) to become mature or tolerogenic through TLRs-dependent signaling pathways, especially TLR4. Regarding the physicochemical properties of biomaterials, some of such signaling pathways are activated. Unsaturated fatty acids have been explored as an antagonist for TLRs and lead to the tolerogenic phenotype of DCs. Here we showed that, although cultured DCs on both chitosan and Alginate-polyethyleneimine (Alg-PEI) films became fully mature, 10-hydroxy-2-decanoic acid (10-HDA), an unsaturated fatty acid found in royal jelly, led to the tolerogenic immunophenotype of DCs on both films. The cultured cells on the films possessed iDCs-like morphology in the presence of 10-HDA. Moreover, 10-HDA expressed lower levels of CD80, CD83, CD86, and HLA-DR, a higher level of IL-10, and lower level of IL-12 in the cultured DCs on both films. Furthermore, HEK293T cells expressing only TLR4 (HEK-TLR4 cells) were co-cultured with LPS, a specific agonist for TLR4, and 10-HDA. The 10-HDA significantly reduced the expression of tumor necrosis factor-a (TNF-alpha) in the HEK-TLR4 cells compared to treated only with LPS. These findings indicate that the 10-HDA acts as an antagonist of TLR4; therefore, potentially can be used in autoimmune diseases and preventing the rejection of biomaterials implantation and allograft transplantation. CI - (c) 2021 Wiley Periodicals LLC. FAU - Eslami-Kaliji, Farshid AU - Eslami-Kaliji F AD - Department of Biomedical Engineering, Faculty of Engineering, University of Isfahan, Isfahan, Iran. AD - Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. FAU - Sarafbidabad, Mohsen AU - Sarafbidabad M AD - Department of Biomedical Engineering, Faculty of Engineering, University of Isfahan, Isfahan, Iran. FAU - Kiani-Esfahani, Abbas AU - Kiani-Esfahani A AD - Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. FAU - Mirahmadi-Zare, Seyede Zohreh AU - Mirahmadi-Zare SZ AUID- ORCID: 0000-0003-1898-7969 AD - Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. FAU - Dormiani, Kianoush AU - Dormiani K AD - Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210227 PL - United States TA - J Biomed Mater Res A JT - Journal of biomedical materials research. Part A JID - 101234237 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Fatty Acids, Monounsaturated) RN - 0 (Immunologic Factors) RN - 0 (Toll-Like Receptor 4) RN - 765-01-5 (10-hydroxy-2-decenoic acid) SB - IM MH - Biomarkers/metabolism MH - Cell Shape/drug effects MH - Cell Survival/drug effects MH - Cytokines/metabolism MH - Dendritic Cells/drug effects/*immunology MH - Fatty Acids, Monounsaturated/*pharmacology MH - HEK293 Cells MH - Humans MH - *Immune Tolerance/drug effects MH - Immunologic Factors/*pharmacology MH - Signal Transduction MH - Spectroscopy, Fourier Transform Infrared MH - *Tissue Engineering MH - Toll-Like Receptor 4/*metabolism OTO - NOTNLM OT - 10-HDA OT - Immunomodulator OT - dendritic cells OT - toll-like receptor 4 OT - unsaturated fatty acid EDAT- 2021/02/28 06:00 MHDA- 2022/02/24 06:00 CRDT- 2021/02/27 08:36 PHST- 2021/02/03 00:00 [revised] PHST- 2020/08/18 00:00 [received] PHST- 2021/02/10 00:00 [accepted] PHST- 2021/02/28 06:00 [pubmed] PHST- 2022/02/24 06:00 [medline] PHST- 2021/02/27 08:36 [entrez] AID - 10.1002/jbm.a.37152 [doi] PST - ppublish SO - J Biomed Mater Res A. 2021 Sep;109(9):1575-1587. doi: 10.1002/jbm.a.37152. Epub 2021 Feb 27.