PMID- 37271505 OWN - NLM STAT- MEDLINE DCOM- 20230606 LR - 20230610 IS - 1976-555X (Electronic) IS - 1229-845X (Print) IS - 1229-845X (Linking) VI - 24 IP - 3 DP - 2023 May TI - In vitro effects of monophosphoryl lipid A and Poly I:C combination on equine cells. PG - e37 LID - 10.4142/jvs.23007 [doi] LID - e37 AB - BACKGROUND: Toll-like receptor (TLR) agonists have been used as adjuvants to modulate immune responses in both animals and humans. OBJECTIVES: The objective of this study was to evaluate the combined effects of the TLR 4 agonist monophosphoryl lipid A (MPL) and the TLR 3 agonist polyinosinic:polycytidylic acid (Poly I:C) on equine peripheral blood mononuclear cells (PBMCs), monocyte-derived dendritic cells (MoDCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs). METHODS: The PBMCs, MoDCs, and BM-MSCs collected from three mixed breed horses were treated with MPL, Poly I:C, and their combination. The mRNA expression of interferon gamma (IFN-gamma), interleukin (IL)-1beta, IL-4, IL-6, IL-8, IL-12p40, tumor necrosis factor alpha (TNF-alpha), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1) was determined using real-time polymerase chain reaction. RESULTS: The combination of MPL and Poly I:C significantly upregulated immunomodulatory responses in equine cells/ without cytotoxicity. The combination induced greater mRNA expression of pro-inflammatory cytokines IFN-gamma and IL-6 than MPL or Poly I:C stimulation alone in PBMCs. In addition, the combination induced significantly higher mRNA expression of IL-1beta, IL-6, and IL-12p40 in MoDCs, and IL-8, MCP-1, and VEGF in BM-MSCs compared to stimulation with a single TLR agonist. CONCLUSIONS: The combination of MPL and Poly I:C can be used as a potential adjuvant candidate for vaccines to aid in preventing infectious diseases in horses. CI - (c) 2023 The Korean Society of Veterinary Science. FAU - Lee, Dong-Ha AU - Lee DH AUID- ORCID: 0000-0002-8898-3632 AD - College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju 63243, Korea. FAU - Lee, Eun-Bee AU - Lee EB AUID- ORCID: 0000-0003-3654-5654 AD - Department of Veterinary Medicine, College of Veterinary Medicine, Jeju National University, Jeju 63243, Korea. FAU - Seo, Jong-Pil AU - Seo JP AUID- ORCID: 0000-0002-6418-9813 AD - Department of Veterinary Medicine, College of Veterinary Medicine, Jeju National University, Jeju 63243, Korea. FAU - Ko, Eun-Ju AU - Ko EJ AUID- ORCID: 0000-0002-1081-904X AD - College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju 63243, Korea. AD - Department of Veterinary Medicine, College of Veterinary Medicine, Jeju National University, Jeju 63243, Korea. eunju@jejunu.ac.kr. LA - eng GR - Jeju National University/Korea PT - Journal Article PL - Korea (South) TA - J Vet Sci JT - Journal of veterinary science JID - 100964185 RN - 0 (Vascular Endothelial Growth Factor A) RN - MWC0ET1L2P (monophosphoryl lipid A) RN - 0 (Interleukin-6) RN - 0 (Interleukin-12 Subunit p40) RN - 0 (Interleukin-8) RN - 0 (Cytokines) RN - 82115-62-6 (Interferon-gamma) RN - 0 (Adjuvants, Immunologic) RN - 0 (RNA, Messenger) RN - 25249-22-3 (Poly I) SB - IM MH - Humans MH - Horses/genetics MH - Animals MH - *Leukocytes, Mononuclear/metabolism MH - *Vascular Endothelial Growth Factor A MH - Interleukin-6 MH - Interleukin-12 Subunit p40 MH - Interleukin-8 MH - Cytokines/genetics/metabolism MH - Interferon-gamma MH - Adjuvants, Immunologic/pharmacology MH - RNA, Messenger MH - Poly I PMC - PMC10244135 OTO - NOTNLM OT - Toll-Like Receptors OT - bone marrow stromal cell OT - dendritic cells OT - immunomodulation OT - peripheral blood mononuclear cell COIS- The authors declare no conflicts of interest. EDAT- 2023/06/05 00:42 MHDA- 2023/06/06 06:42 PMCR- 2023/05/01 CRDT- 2023/06/04 20:52 PHST- 2023/01/04 00:00 [received] PHST- 2023/02/09 00:00 [revised] PHST- 2023/03/10 00:00 [accepted] PHST- 2023/06/06 06:42 [medline] PHST- 2023/06/05 00:42 [pubmed] PHST- 2023/06/04 20:52 [entrez] PHST- 2023/05/01 00:00 [pmc-release] AID - 24.e37 [pii] AID - 10.4142/jvs.23007 [doi] PST - ppublish SO - J Vet Sci. 2023 May;24(3):e37. doi: 10.4142/jvs.23007.