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

Jon Andoni Sánchez, Amparo Alfonso, Ines Rodriguez, Eva Alonso, José Manuel Cifuentes, Roberto Bermudez, Mostafa E Rateb, Marcel Jaspars, Wael E Houssen, Rainer Ebel, Jioji Tabudravu, Luís M Botana

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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.

Original languageEnglish
Article number452
JournalFrontiers in Immunology
Volume7
DOIs
Publication statusPublished - 24 Oct 2016

Fingerprint

Cyclophilin A
Ear
T-Lymphocytes
Inflammation Mediators
Membranes
Immune System Diseases
Porifera
Immunosuppressive Agents
Cyclosporine
Cell Movement
Immune System
Inflammation
Neoplasms

Keywords

  • Spongionella sp.
  • CD147
  • cyclophilin A
  • inflammation
  • chemotaxis

Cite this

Sánchez, J. A., Alfonso, A., Rodriguez, I., Alonso, E., Cifuentes, J. M., Bermudez, R., ... Botana, L. M. (2016). Spongionella Secondary Metabolites, Promising Modulators of Immune Response through CD147 Receptor Modulation. Frontiers in Immunology, 7, [452]. https://doi.org/10.3389/fimmu.2016.00452

Spongionella Secondary Metabolites, Promising Modulators of Immune Response through CD147 Receptor Modulation. / Sánchez, Jon Andoni; Alfonso, Amparo; Rodriguez, Ines; Alonso, Eva; Cifuentes, José Manuel; Bermudez, Roberto; Rateb, Mostafa E; Jaspars, Marcel; Houssen, Wael E; Ebel, Rainer; Tabudravu, Jioji; Botana, Luís M.

In: Frontiers in Immunology, Vol. 7, 452, 24.10.2016.

Research output: Contribution to journalArticle

Sánchez, Jon Andoni ; Alfonso, Amparo ; Rodriguez, Ines ; Alonso, Eva ; Cifuentes, José Manuel ; Bermudez, Roberto ; Rateb, Mostafa E ; Jaspars, Marcel ; Houssen, Wael E ; Ebel, Rainer ; Tabudravu, Jioji ; Botana, Luís M. / Spongionella Secondary Metabolites, Promising Modulators of Immune Response through CD147 Receptor Modulation. In: Frontiers in Immunology. 2016 ; Vol. 7.
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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.",
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note = "Acknowledgments The research leading to these results has received funding from the following FEDER cofounded-grants. From CDTI and Technological Funds, supported by Ministerio de Econom{\'i}a y Competitividad, AGL2012-40185-CO2-01, AGL2014-58210-R, and Conseller{\'i}a de Cultura, Educaci{\'o}n e Ordenaci{\'o}n Universitaria, GRC2013-016, and through Axencia Galega de Innovaci{\'o}n, Spain, ITC-20133020 SINTOX. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD. From the European Union’s Seventh Framework Programme managed by REA – Research Executive Agency (FP7/2007-2013) under grant agreement 312184 PHARMASEA. We wish to thank the Cl{\'i}nica Losada Arr{\'a}nz, especially Ms. Paula L{\'o}pez Arr{\'a}nz for providing the human blood samples for T cells purification. JS is supported by a fellowship from Plan Galego de Investigaci{\'o}n e Crecemento, Xunta de Galicia, Spain.",
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AU - Sánchez, Jon Andoni

AU - Alfonso, Amparo

AU - Rodriguez, Ines

AU - Alonso, Eva

AU - Cifuentes, José Manuel

AU - Bermudez, Roberto

AU - Rateb, Mostafa E

AU - Jaspars, Marcel

AU - Houssen, Wael E

AU - Ebel, Rainer

AU - Tabudravu, Jioji

AU - Botana, Luís M

N1 - Acknowledgments The research leading to these results has received funding from the following FEDER cofounded-grants. From CDTI and Technological Funds, supported by Ministerio de Economía y Competitividad, AGL2012-40185-CO2-01, AGL2014-58210-R, and Consellería de Cultura, Educación e Ordenación Universitaria, GRC2013-016, and through Axencia Galega de Innovación, Spain, ITC-20133020 SINTOX. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD. From the European Union’s Seventh Framework Programme managed by REA – Research Executive Agency (FP7/2007-2013) under grant agreement 312184 PHARMASEA. We wish to thank the Clínica Losada Arránz, especially Ms. Paula López Arránz for providing the human blood samples for T cells purification. JS is supported by a fellowship from Plan Galego de Investigación e Crecemento, Xunta de Galicia, Spain.

PY - 2016/10/24

Y1 - 2016/10/24

N2 - 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.

AB - 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.

KW - Spongionella sp.

KW - CD147

KW - cyclophilin A

KW - inflammation

KW - chemotaxis

U2 - 10.3389/fimmu.2016.00452

DO - 10.3389/fimmu.2016.00452

M3 - Article

VL - 7

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 452

ER -