A Functional Network Driven by MicroRNA-125a Regulates Monocyte Trafficking in Acute Inflammation

Tomasi, Stephanie; Li, Lei; Hinske, Ludwig Christian; Tomasi, Roland; Amini, Martina; Strauß, Gabriele; Müller, Martin Bernhard; Hirschberger, Simon; Peterss, Sven; Effinger, David; Pogoda, Kristin; Kreth, Simone; Hübner, Max (2022): A Functional Network Driven by MicroRNA-125a Regulates Monocyte Trafficking in Acute Inflammation. International Journal of Molecular Sciences, 23 (18): 10684. ISSN 1422-0067

Abstract

During the onset of acute inflammation, rapid trafficking of leukocytes is essential to mount appropriate immune responses towards an inflammatory insult. Monocytes are especially indispensable for counteracting the inflammatory stimulus, neutralising the noxa and reconstituting tissue homeostasis. Thus, monocyte trafficking to the inflammatory sites needs to be precisely orchestrated. In this study, we identify a regulatory network driven by miR-125a that affects monocyte adhesion and chemotaxis by the direct targeting of two adhesion molecules, i.e., junction adhesion molecule A (JAM-A), junction adhesion molecule-like (JAM-L) and the chemotaxis-mediating chemokine receptor CCR2. By investigating monocytes isolated from patients undergoing cardiac surgery, we found that acute yet sterile inflammation reduces miR-125a levels, concomitantly enhancing the expression of JAM-A, JAM-L and CCR2. In contrast, TLR-4-specific stimulation with the pathogen-associated molecular pattern (PAMP) LPS, usually present within the perivascular inflamed area, resulted in dramatically induced levels of miR-125a with concomitant repression of JAM-A, JAM-L and CCR2 as early as 3.5 h. Our study identifies miR-125a as an important regulator of monocyte trafficking and shows that the phenotype of human monocytes is strongly influenced by this miRNA, depending on the type of inflammatory stimulus.

• Dokumententyp: Artikel (Klinikum der LMU)
• Organisationseinheit (Fakultäten): 07 Medizin > Klinikum der LMU München > Klinik für Anaesthesiologie
• DFG-Fachsystematik der Wissenschaftsbereiche: Lebenswissenschaften
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 413635475
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892