Danger-associated molecular patterns (DAMPs) are released on the onset of tissue injury or death, which tend to trigger innate immunity and regulate various immune pathways. Among the various DAMP molecules, S100A8 and S100A9 belonging to Ca binding proteins with EF-hands and Zn ion binding sites have been implicated in aggravating the pathogenesis of rheumatoid arthritis (RA), upon interaction with pattern recognition receptors (PRR) such as TLR4, RAGE and CD36 receptors. Thus, the present study aims to assess the effect of Ca or Zn ions on the interaction of S100A8 and S100A9 proteins towards the PRRs. Protein-protein interaction analysis showed that the TLR4-S100A8CaZn, TLR4-S100A8 Zn, RAGE-S100A8/A8Zn, RAGE-S100A8/A8Ca, CD36-S100A8Ca, and CD36-S100A9/A9Ca showed higher affinity against each other. The 100 ns molecular dynamics simulation showed that the TLR4-S100A8Ca, RAGE-S100A8/A8Ca and CD36-S100A8Ca complexes showed minimal fluctuations in their trajectory indicating that Ca bound complexes were more stable than the other complexes. Furthermore, SPR analysis showed that S100A9 exhibited higher binding affinity towards PRRs in the presence of Ca and Zn ions. Considering the fact that physiological levels of both Ca and Zn ions play a critical role in the binding of S100A8 and S100A9 proteins against the PRRs, it can be emphasized that the S100A9 and RAGE receptors could be the critical players in the RA pathogenesis due to its impeccable binding towards the PRRs in the presence of both Ca and Zn ions. Nonetheless, further in vivo, and in vitro studies are imperative to validate these findings and identify potential targets for RA treatment.
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http://dx.doi.org/10.1007/s12013-024-01600-6 | DOI Listing |
Elife
December 2024
Walter Brendel Center of Experimental Medicine, Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Ludwig-Maximilians-University, Planegg-Martinsried, München, Germany.
S100A8/A9 is an endogenous alarmin secreted by myeloid cells during many acute and chronic inflammatory disorders. Despite increasing evidence of the proinflammatory effects of extracellular S100A8/A9, little is known about its intracellular function. Here, we show that cytosolic S100A8/A9 is indispensable for neutrophil post-arrest modifications during outside-in signaling under flow conditions in vitro and neutrophil recruitment in vivo, independent of its extracellular functions.
View Article and Find Full Text PDFPhytomedicine
November 2024
Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China; Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, PR China. Electronic address:
Front Biosci (Landmark Ed)
November 2024
Laboratory of Human Molecular Genetics, National Research Center "Kurchatov Institute", 123182 Moscow, Russia.
Background: The associations of high-density lipoprotein (HDL) level and functionality with lipid metabolism, inflammation, and innate immunity in coronary artery disease (CAD) remain controversial. The differential expression of a set of genes related to HDL metabolism (24 genes) and atherogenesis (41 genes) in peripheral blood mononuclear cells (PBMC) from CAD and control patients with varied HDL cholesterol (HDL-C) levels was compared.
Methods: 76 male patients 40-60 years old with CAD diagnosed by angiography and 63 control patients were divided into three groups with low, normal (1.
Int Immunopharmacol
January 2025
Department of Dermatology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China; General Practice Department, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. Electronic address:
Pharmacol Res
December 2024
Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, China. Electronic address:
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