Spongionella Secondary Metabolites, Promising Modulators of Immune Response through CD147 Receptor Modulation

Abstract

The modulation of the immune system can have multiple applications such as cancer treatment, and a wide type of processes involving inflammation where the potent chemotactic agent cyclophilin A (Cyp A) is implicated. The Porifera phylum, in which Spongionella is encompassed, is the main producer of marine bioactive compounds. Four secondary metabolites obtained from Spongionella (Gracilin H, A, L, and Tetrahydroaplysulphurin-1) were described to hit Cyp A and to block the release of inflammation mediators. Based on these results, some role of Spongionella compounds on other steps of the signaling pathway mediated by this chemotactic agent can be hypothesized. In the present paper, we studied the effect of these four compounds on the surface membrane CD147 receptor expression, on the extracellular levels of Cyp A and on the ability to migrate of concanavalin (Con A)-activated T lymphocytes. Similar to a well-known immunosuppressive agent cyclosporine A (CsA), Gracilin H, A, L, and tetrahydroaplysulphurin-1 were able to reduce the CD147 membrane expression and to block the release of Cyp A to the medium. Besides, by using Cyp A as chemotactic agent, T cell migration was inhibited when cells were previously incubated with Gracilin A and Gracilin L. These positive results lead us to test the in vivo effect of Gracilin H and L in a mouse ear delayed hypersensitive reaction. Thus, both compounds efficiently reduce the ear swelling as well as the inflammatory cell infiltration. These results provide more evidences for their potential therapeutic application in immune-related diseases of Spongionella compounds.

A Critical Role of Peptidylprolyl Isomerase A Pseudogene 22/microRNA-197-3p/Peptidylprolyl Isomerase A Axis in Hepatocellular Carcinoma

“…PPIase is regarded as a chaperone and can work with other chaperone proteins ( Luban, 1996 ). Besides, PPIA has been found to respond to immune and inflammatory stimuli and considered to be an important protein recently ( Nigro et al, 2013 ; Sánchez et al, 2016 ).…”

“…The enrichment analysis of protein-protein interaction showed a prominent role of PPIA in regulating mRNA metabolic process and some pathways involved in tumor immunity. Several studies have proved that PPIA is related to the regulation of the immune system, and it can have many applications, such as cancer treatment and various processes involving inflammation ( Sánchez et al, 2016 ). In breast cancer, the pharmacological inhibition of PPIA may provide promising and unexpected results in cancer biology, in part by targeting the PPIA/CrkII axis that can modulate the host antitumor immune escape ( Davra et al, 2020 ).…”

Marine natural products

“…502 The common spongian diterpenoids gracilin A, 503,504 H, 505 and L, 506 and additionally tetrahydroaplysulphurin-1, 507 bound strongly to cyclophilin A in a manner similar to cyclosporine A, and hence are new immunosuppressants. 508,509 The highly oxygenated diterpenoid gagunin D 510 inhibited melanin production through inhibition of tyrosinase expression, making it a potential skin whitening cosmetic agent. 511 A large number of rst syntheses have been reported in 2016, including vesparioside B, 512,513 strongylodiols C and D, 514,515 lembehyne B, 516,517 the previously unreported xestospongenyne, 518 and petrosiol A.…”

Predicting Blood–Brain Barrier Permeability of Marine-Derived Kinase Inhibitors Using Ensemble Classifiers Reveals Potential Hits for Neurodegenerative Disorders

“…According to our best models, none of these marine compounds were predicted to pass the BBB, with GBC-based probability estimates inferior than 0.01. Gracilin A analogues were not detected in murine brain and blood matrices [ 51 ]. Synthetic derivatives of leucettamine B, leucettines, e.g., L41, displayed neuroprotective properties and corrected cognitive deficits in mouse models of Down syndrome [ 52 , 53 ].…”