Abstract
Sepsis is a disease that is characterized by a severe systemic inflammatory response to microbial infection and lipopolysaccharide (LPS) and is a well-known inducer of sepsis, as well as endothelial cell hyperpermeability. In the present study, we confirm the elevation of CXC chemokine ligand 13 (CXCL13) in sepsis patients. We also show that LPS exposure increases the release of CXCL13, as well as the mRNA and protein expression of CXCL13 and its receptor, CXC chemokine receptor 5 (CXCR5) in human umbilical vein endothelial cells (HUVECs) in a dose- and time-dependent manner. We also examined the effects of CXCL13 knockdown on LPS-mediated endothelial hyperpermeability and tight junction (TJ) protein expression in HUVECs. Our results show that HUVECs exposed to LPS result in a significant decrease in transendothelial electrical resistance (TER) and TJ protein (Zonula occluden-1, occludin, and claudin-4) expression, and a notable increase in fluorescein isothiocyanate (FITC)-dextran flux and p38 phosphorylation, which was partially reversed by CXCL13 knockdown. Recombinant CXCL13 treatment had a similar effect as LPS exposure, which was attenuated by a p38 inhibitor, SB203580. Moreover, the CXCL13-neutralizing antibody significantly increased the survival rate of LPS-induced sepsis mice. Collectively, our results show that CXCL13 plays a key role in LPS-induced endothelium hyperpermeability via regulating p38 signaling and suggests that therapeutically targeting CXCL13 may be beneficial for the treatment of sepsis.
Highlights
Sepsis is a disease characterized by a severe systemic inflammatory response to microbial infection [1]
The Expression of CXC chemokine ligand 13 (CXCL13)/CXC chemokine receptor 5 (CXCR5) Was Increased by LPS Exposure in a Dose- and Time-Dependent Manner
The results showed that LPS exposure increased the release of CXCL13 (Fig. 2D), as well as mRNA (Fig. 2E) and protein (Fig. 2F) levels of CXCL13/CXCR5 in a time-dependent manner
Summary
Sepsis is a disease characterized by a severe systemic inflammatory response to microbial infection [1]. Most of the septic response is caused by endotoxin or lipopolysaccharide (LPS), the cell wall component of. Inflammatory mediators and free radicals, produced by the septic response, activate endothelial cells, which lead to endothelial damage in sepsis [5,6,7,8]. The endothelium forms a barrier that selectively controls the delivery of solutes, proteins, and cells [9], and LPSinduced endothelial hyperpermeability is a major cause of sepsis [10]. Decreased expression of ZO-1 and occludin was observed in human vascular endothelial cells treated with LPS [17]. The molecular mechanisms that regulate this process are not fully understood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
