1.Lipoxin A4 prevents tight junction disruption and delays the colonisation of cystic fibrosis bronchial epithelial cells by Pseudomonas aeruginosa.
Higgins G1, Fustero Torre C2, Tyrrell J3, McNally P4, Harvey BJ5, Urbach V6. Am J Physiol Lung Cell Mol Physiol. 2016 Apr 15:ajplung.00368.2015. doi: 10.1152/ajplung.00368.2015. [Epub ahead of print]
The specialised pro-resolution lipid mediator, lipoxin A4 (LXA4), is abnormally produced in cystic fibrosis (CF) airways. LXA4increases the CF airway surface liquid height and stimulates airway epithelial repair and tight junction formation. We report here, a protective effect of LXA4(1nM) against tight junction disruption caused by Pseudomonas aeruginosa bacterial challenge together with a delaying action against bacterial invasion in CF airway epithelial cells from patients with CF and immortalised cell lines. Bacterial invasion and tight junction integrity were measured using gentamicin exclusion assays and confocal fluorescence microscopy in non-CF (NuLi-1) and CF (CuFi-1) bronchial epithelial cell lines and in primary CF cultures, grown under an air/liquid interface, exposed to either a clinical or laboratory strains of P. aeruginsosa. LXA4delayed P. aeruginosa, invasion and transepithelial migration in CF and normal bronchial epithelial cell cultures.
2.Easy access to constrained peptidomimetics and 2,2-disubstituted azetidines by the unexpected reactivity profile of α-lithiated N-Boc-azetidines.
Parisi G1, Capitanelli E, Pierro A, Romanazzi G, Clarkson GJ, Degennaro L, Luisi R. Chem Commun (Camb). 2015 Nov 4;51(85):15588-91. doi: 10.1039/c5cc06323j.
The reactivity profile of lithiated N-Boc-2-arylazetidines has been investigated filling a gap in the chemistry of this class of four-membered heterocycles. Two unexpected and unprecedented results have been observed: an "ortho-effect" accounting for the regioselective functionalization of the azetidine ring, and self-condensation leading to new and interesting azetidine-based peptidomimetics.
3.The synthesis of sulforaphane analogues and their protection effect against cisplatin induced cytotoxicity in kidney cells.
Kim T1, Kim YJ, Han IH, Lee D, Ham J, Kang KS, Lee JW. Bioorg Med Chem Lett. 2015 Jan 1;25(1):62-6. Epub 2014 Nov 11.
A series of sulforaphane analogues were synthesized with various amines by treatment of carbon disulfide followed by Boc₂O and DMAP. These synthesized sulforaphane analogues were tested on cisplatin treated cultured LLC-PK1 kidney cell line. Among these analogues, several compounds including SF5 show a potent effect on kidney cell protection assay at the concentration of 2.5 μM. Further studies with compound SF5 revealed that the kidney cell protection effect was related by inhibiting the apoptosis pathway through JNK-p53-caspase apoptotic cascade. Compound SF5 may be considered as a promising candidate for the development of new kidney protection agent against drug induced acute kidney disease.
4.Lipoxin A4 suppresses lipopolysaccharide-induced hela cell proliferation and migration via NF-κB pathway.
Hao H1, Xu F, Hao J, He YQ, Zhou XY, Dai H, Wu LQ, Liu FR. Inflammation. 2015 Feb;38(1):400-8. doi: 10.1007/s10753-014-0044-6.
Uterine cervical carcinoma (UCC) is one of the most common malignant tumors in females, and UCC has a close relationship with chronic cervicitis. As the endogenous "braking signal," lipoxins can regulate anti-inflammation and the resolution of inflammation. We investigated the effect of lipoxin A4 (LXA4) on the proliferation, apoptosis, and migration in lipopolysaccharide (LPS)-stimulated Hela cells. We demonstrated that LXA4 could significantly suppress p53, cyclin D1 expression, and migration of LPS-stimulated Hela cells via nuclear factor-κB (NF-κB) pathway, and these effects could be blocked by Boc-2, the specific inhibitor of FPR2/ALX (the receptor of LXA4). We presented evidence for a novel role of LXA4 on the proliferation and migration in LPS-stimulated Hela cells, and FPR2/ALX was involved in the procedures. These results showed that LXA4 could be a possible candidate for UCC therapy, and blocking the activation of NF-κB would be an effective drug target.
