Accumulating lines of evidence suggest that retinoic acid receptor agonists such as Am80 exerts anti-inflammatory actions in the central nervous system, although detailed mechanisms of the action remain largely unknown. Our previous findings suggest that Am80 provides therapeutic effect on intracerebral hemorrhage in mice via suppression of expression of chemokine (C-X-C motif) ligand 2 (CXCL2). Here we investigated the mechanisms of inhibitory action of Am80 on expression of CXCL2 and other pro-inflammatory factors in microglial BV-2 cells. Pretreatment with Am80 markedly suppressed lipopolysaccharide (LPS)-induced expression of CXCL2 mRNA and release of CXCL2 protein. Am80 had no effect on LPS-induced activation of p38 mitogen-activated protein kinase and extracellular signal-regulated kinase. On the other hand, Am80 prevented LPS-induced nuclear translocation of p65 subunit of NF-κB complex. In addition, total expression levels of p65 and IκBα proteins, as well as of mRNAs encoding p65 and IκBα, were lowered by Am80. Dependence of CXCL2 expression on NF-κB was confirmed by the effect of an NF-κB inhibitor caffeic acid phenethyl ester that abolished LPS-induced CXCL2 expression. Caffeic acid phenethyl ester also abolished LPS-induced expression of inducible nitric oxide synthase, interleukin-1β and tumor necrosis factor α, which may be relevant to the inhibitory effect of Am80 on expression of these pro-inflammatory factors. We additionally found that Am80 attenuated LPS-induced up-regulation of CD14, a co-receptor for Toll-like receptor 4 (TLR4). These results suggest that inhibitory effect on TLR4 signaling mediated by NF-κB pathway underlies the anti-inflammatory action of retinoic acid receptor agonists in microglia.
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http://dx.doi.org/10.1016/j.intimp.2016.06.025 | DOI Listing |
J Oral Biosci
January 2025
Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, Korea. Electronic address:
Objectives: We investigated the involvement of FOXO3a in lipopolysaccharide (LPS)-induced inflammation in primary human dental pulp cells (HDPCs).
Methods: HDPCs that were isolated from donors undergoing tooth extraction for orthodontic purposes were cultured with or without 1 μg/mL LPS at various intervals. The FOXO3a localization in the HDPCs was verified using immunofluorescence.
Toxicol Res (Camb)
February 2025
Département Toxicologie et Biométrologie, Institut National de Recherche et de Sécurité pour la prévention des accidents du travail et des maladies professionnelles (INRS), 1 rue du Morvan, 54519 Vandœuvre-lès-Nancy, France.
In many industrial activities, workers may be exposed by inhalation to particles that are aerosolized, To predict the human health hazard of these materials, we propose to develop a co-culture model (macrophages, granulocytes, and alveolar epithelial cells) designed to be more representative of the inflammatory pulmonary response occurring in vivo. Phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells were used as macrophages, All-trans retinoic acid (ATRA)-differentiated HL60 were used as granulocytes and A549 were used as epithelial alveolar type II cells. A crystalline silica sample DQ12 was used as a prototypical particle for its capabilities to induce DNA damage, inflammatory response, and oxidative stress in epithelial cells; its polyvinylpyridine-N-oxide (PVNO)-surface modified counterpart was also used as a negative particulate control.
View Article and Find Full Text PDFScand J Immunol
January 2025
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
The effects of vitamin D and vitamin A in immune cells are mediated through the vitamin D receptor (VDR) and retinoic acid receptor (RAR), respectively. These receptors share the retinoid X receptor (RXR) co-factor for transcriptional regulation. We investigated the effects of active vitamin D (1,25(OH)D) and 9-cis retinoic acid (9cRA) on T helper (T)1 and T2 cytokines and transcription factors in primary human blood-derived CD4 T cells.
View Article and Find Full Text PDFArch Dermatol Res
January 2025
Department of Dermatology, Hitit University, Erol Olçok Training and Research Hospital, Çorum, Türkiye.
Curr Mol Med
January 2025
Department of Neonatology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China.
Objective: This study aimed to investigate the roles of Mucin 1 (MUC1), the PI3K/AKT pathway, and enterocyte apoptosis in Necrotizing Enterocolitis (NEC).
Methods: Using an NEC Caco-2 cell model, retinoic acid treatment and MUC1 gene silencing were employed. Flow cytometry was used to assess apoptosis, while quantitative PCR and western blot analyses were conducted to evaluate the gene and protein expressions of MUC1, PI3K, Akt, and factors related to apoptotic modulation.
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