Cholesteryl butyrate solid lipid nanoparticles inhibit adhesion of human neutrophils to endothelial cells

Abstract

1 Adhesion of polymorphonuclear cells (PMNs) to vascular endothelial cells (EC) is a critical step in recruitment and infiltration of leukocytes into tissues during inflammation. High doses of butyric acid have been shown to ameliorate inflammation in inflammatory bowel diseases (IBD). Cholesteryl-butyrate solid lipid nanoparticles (chol-but SLN) as prodrug are a possible delivery system for butyric acid. 2 Sodium butyrate or chol-but SLN were coincubated with human PMNs and human umbilical vein EC (HUVEC); adhesion was quantified by computerized microimaging fluorescence analysis. Both chol-but SLN and sodium butyrate displayed antiadhesive effects on FMLP-and IL-1b-stimulated cells in a concentration-response curve (10 À8 -10 À5 M), but chol-but SLN were in all cases more active. Moreover, chol-but SLN inhibited FMLP-induced adhesion of PMNs to FCS-coated plastic wells, thus showing a direct effect on PMNs, while sodium butyrate had little effect. Confocal microscopy showed that fluorescent SLN entered PMNs and HUVEC after 10 min incubation. Chol-but SLN acted either on activated PMN or HUVEC. 3 Chol-but SLN inhibited O 2 À Á production and myeloperoxidase release by PMNs evoked by FMLP, in a dose-dependent, but not time-dependent, manner and were more active than sodium butyrate. 4 In conclusion, in all tests chol-but SLN were more active than sodium butyrate. Thus, chol-but SLN might be a valid alternative to sodium butyrate in the anti-inflammatory therapy of ulcerative colitis, avoiding complications related to the administration of sodium butyrate.

Effects of short chain fatty acids on effector mechanisms of neutrophils

“…1,40,41 The effect of butyrate on PMA-and fMLP-induced ROS production by neutrophils was previously reported by others. 14,17,19,21 The inhibition of ROS production by butyrate reported herein was not due to modulation of expression of NADPH oxidase components, but it was associated to reduced phosphorylation of the regulatory subunit p47phox. The inhibitory effect of butyrate on 42 GPR43 can be activated by SCFAs and is highly expressed in neutrophils and monocytes being coupled to Gi/o and Gq proteins.…”

The Role of the Microbial Metabolites Including Tryptophan Catabolites and Short Chain Fatty Acids in the Pathophysiology of Immune-Inflammatory and Neuroimmune Disease

“…For example, G protein-coupled receptor-41 and G protein-coupled receptor-43 are activated by almost all SCFAs [78] and are expressed at physiological levels on enteroendocrine cells and normal enterocytes [79][80][81][82]. G protein-coupled receptor-41 is also present on the cell membranes of other cells such as adipocytes, pancreatic cells, and enteric neuronal cells [83,84]. Extraintestinal expression of G protein-coupled receptor-43 appears on some myeloid cells and all granulocytes [85,86].…”

Nanomedicine development for autoimmune diseases

“…This was thought to occur by reducing their capability to adhere to endothelial cells, production of superoxide anion (O À 2 ), and release of myeloperoxidase [Dianzani et al, 2006]. Dexamethasone-incorporating SLNs had a higher efficiency in inhibiting LPS-stimulated PMNs to secrete pro-inflammatory cytokines (90% reduction), including IL-1b and TNF-a than dexamethasone alone (25% reduction) [Serpe et al, 2010].…”