Background/objective: Malondialdehyde-acetaldehyde adducts (MAA) act as potent immune adjuvants and co-localize with citrullinated antigens in tissues effected by rheumatoid arthritis (RA). We sought to examine the role of MAA-adducts in promoting RA-related autoimmunity and inflammation.
Methods: DBA/J1 mice were immunized with human serum albumin (HSA), HSA-MAA, citrullinated HSA (HSA-Cit), or HSA-MAA-Cit with subsequent measurement of serum anti-citrullinated protein antibody (ACPA) and anti-Cit T cell responses. Cellular binding of the same antigens was examined using THP-1 monocytes and Chinese Hamster Ovary (CHO) cells transfected with specific scavenger receptors (SRs: TLR4, SR-B2, SREC-1). The effects of these antigens on THP-1 activation were then examined by quantifying plate adherence, pro-inflammatory (TNFα, IL-1β, IL-10) cytokine release, and SR (CD14, SR-B2)/co-stimulatory molecule (CD80, HLA-DR) expression. Comparisons were completed using one-way ANOVA with Tukey's post-hoc test.
Results: Mice immunized with co-modified HSA produced significantly higher ACPA concentrations than all other groups whereas T cell responses to citrullinated proteins were highest following immunization with HSA-MAA. Both transfected CHO and THP-1 cells demonstrated significantly higher binding of HSA-MAA-Cit vs. HSA or HSA-Cit. THP-1 cells exposed to HSA-MAA-Cit expressed significantly higher concentrations of TNFα, IL-1β, and IL-10 vs. all other groups. Furthermore, THP-1 cells demonstrated significantly increased plate adherence and higher expression of CD14, SR-B2, and HLA-DR following incubation with HSA-MAA-Cit vs. HSA or HSA-Cit.
Conclusion: These studies demonstrate that MAA-adduction of citrullinated antigen greatly enhances immune and cellular responses, potentially acting as a key co-factor in RA pathogenesis.
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http://dx.doi.org/10.1016/j.intimp.2020.106433 | DOI Listing |
J Nat Prod
January 2025
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Bibenzyls and dihydrophenanthrenes exhibit promising immunomodulatory effects in various human diseases. In this study, we isolated one new dihydrophenanthrene derivative (), two new bibenzyl-dihydrophenanthrene derivatives () along with 12 known compounds (-) from the methanol extract of . These compounds were identified by using physicochemical analyses and spectroscopic methods.
View Article and Find Full Text PDFFront Cell Infect Microbiol
January 2025
Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
is a prevalent fungal pathogen responsible for infections in humans. As described recently, nanometer-sized extracellular vesicles (EVs) produced by play a crucial role in the pathogenesis of infection by facilitating host inflammatory responses and intercellular communication. This study investigates the functional properties of EVs released by biofilms formed by two strains-3147 (ATCC 10231) and SC5314-in eliciting host responses.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou 646000 Sichuan, China. Electronic address:
Background: Peri-implantitis is an inflammatory bone disease that seriously affects the health of dental implants. Pyroptosis plays an important role in peri-implantitis and inhibition of pyroptosis may point out a new direction for treating the disease. The long non-coding RNA Negative Regulator of Interferon Response (lncRNA NRIR) is closely related to peri-implantitis and may be involved in the process of pyroptosis.
View Article and Find Full Text PDFAnn Allergy Asthma Immunol
January 2025
Department of Otorhinolaryngology Head and Neck Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:
Background: Recent studies show that M1 macrophages accumulate predominantly in non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP). However, the precise mechanisms regulating M1 macrophages and their impact on the epithelial barrier remain unclear.
Objective: We aim to investigate the expression and regulatory role of SLAMF8, a molecule exclusively expressed in myeloid cells, in M1 macrophage polarization and its potential contribution to neCRSwNP development.
Int Immunopharmacol
January 2025
Department of Immunology, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, China. Electronic address:
Objective: Aberrant 6-phosphofructo-2kinase/fructose-2,6-bisphoshatase 3 (PFKFB3) expression is tightly correlated with multiple steps of tumorigenesis; however, the pathological significance of PFKFB3 in macrophages in patients with rheumatoid arthritis (RA) remains obscure. In this study, we examined whether PFKFB3 modulates macrophage activation and promotes RA development.
Method: Peripheral blood mononuclear cells (PBMCs) from patients with RA, THP-1 cells, and bone marrow-derived macrophages from conditional PFKFB3-knockout mice were used to investigate the mechanism underlying PFKFB3-induced macrophage regulation of RA.
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