Lactobacillus helveticus HY7801 Attenuates Inflammatory Edema and Vascular Leakage while Modulating Endothelial Barrier Responses.

Abstract

Tissue edema results from excessive interstitial fluid accumulation driven by inflammatory responses and increased vascular leakage. This study investigated the protective effects of Lactobacillus helveticus HY7801 (HY7801) against inflammatory activation, endothelial barrier dysfunction, and edema formation in vitro and in vivo. In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, HY7801 reduced nitrite accumulation and iNOS expression. In tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs), HY7801 increased nitrite accumulation and eNOS expression, suppressed the expression of endothelial adhesion molecules (ICAM1, VCAM1, and SELE) and CXCL8, and enhanced the expression of the tight junction-associated genes (TJP1 and CLDN5). Furthermore, HY7801 partially restored transendothelial electrical resistance (TEER), an indicator of endothelial barrier integrity, following TNF-α-induced impairment. In a λ-carrageenan-induced mouse paw edema model, HY7801 treatment attenuated paw swelling, histological tissue thickening, and vascular leakage. These effects were accompanied by increased junction-associated gene expression in inflamed paw tissue and reduced circulating inflammatory mediators. Based on these anti-inflammatory and endothelial barrier-protective effects, HY7801-derived extracellular vesicles (HY7801 EVs) were further evaluated in vitro as a candidate bioactive component of HY7801. HY7801 EVs enhanced TJP1 and CLDN5 expression while suppressing ICAM1, VCAM1, and SELE expression. Collectively, our findings suggest that HY7801 attenuates inflammation-associated tissue edema and vascular leakage through coordinated modulation of inflammatory and endothelial barrier responses, and support a potential role for HY7801 EVs as a bioactive component contributing to these effects.