The group "Pharmacology of Inflammation", Department of Pharmacology, Universitat de València is focused on the inflammatory process and new therapeutic targets for the treatment of many inflammatory diseases with a high repercusion in our society.

Therefore, we have developed at the preclinical stage new antiinflammatory agents possessing mechanisms of action different from those of marketed drugs and that represent new approaches for the control of inflammatory processes. Some of these compounds are of natural origin, such as several marine metabolites isolated from sponges with inhibitory activity on phospholipase A2 (patent CNR Italia-University of Valencia, 1996) or reducing the activativation of nuclear factor kB and the transcription of inflammatory genes. We have also found new families of antiinflammatory agents obtained by chemical synthesis which are inhibitors of lipoxygenase and cyclooxygenase. They have been developed within FEDER and PETRI projects.

In addition, we have demonstrated the protective role of heme oxygenase-1 in inflammation, which offers new perspectives in the treatment of a large number of diseases. Therefore, we have established the induction of this protein in animal models of inflammation as well as in patients from osteoarthritis and rheumatoid arthritis. We have also studied its regulation by mediators such as pro-inflammatory and antiinflammatory cytokines and its relationships with cyclooxygenase-2 and nitric oxide, as well as the conditions and mechanisms involved in its pharmacological induction.

We are interested in the physiopathological processes responsible for inflammatory and degenerative conditions and their modulation. We have an important expertise in the study of antiinflammatory agents working in multidisciplinary projects in collaboration with European institutions specialist in Chemistry (Prof. Molina, University of Murcia, Dr. De Rosa, CNRS, Naples, Dr. D'Auria, University of Naples, Prof. Sodano and Dr. Gomez Paloma, University of Salerno). We have also collaborated with Prof. Van den Berg (Nijmegen University Hospital) and Prof. Cronstein (NYU Medical School) for the development of models of inflammatory diseases. We have cooperated with Prof. Facchini (Istituto Ortopédico Ruzzoli, Bolonia) and Dr. Goldring (Harvard Institutes of Medicine) in cultures of human chondrocytes, and with Dr. Habib (American University of Beirut) in cellular protective mechanisms. Dr. Payá has collaborated last year with Institut Pasteur (Paris) in phospholipases A2 studies (Dr. Touqui).

We are aware of the relevance of scientific education and have supervised twelve Ph.D thesis in the last five years. The doctorate programme of our Department has received last year the "Quality Mention" from the Ministery of Education and Science. Extraordinary awards have been granted to four of our doctors in the last five years and two of them have received the Ramón y Cajal fellowship (Ministery of Education and Science) in the last year (Drs. Montesinos and Posadas). Others follow a research career, like Dr. Lucas (post-doctoral fellowship, Imperial College School of Medicine, UK and at present at CSAT, Valencia) and Drs. Rioja (Marie Curie fellowship, Glaxo, UK), Devesa (Marie Curie fellowship, Bioxell spA, Milano) and Fernandez (postdoctoral fellow, NYU Medical School). Funded by ALFA Programme, U.E., a number of American students have finished their doctoral studies with us, like Dr. L.F. Ospina, professor in the National University of Colombia, Dr. E. De León, lecturer in the University of Panamá and Dr. Javier Rojas (University of Chile, at present postdoctoral fellow, University of Aberdeen). Dr. Jérôme Busserolles has worked in our group for two years with a Marie Curie host development contract.

AWARDS:
Dr. Esteve FOUNDATION RESEARCH AWARD (2001).
Best oral communication Award (Spanish Society of Pharmacology, 2004).

INTERNATIONAL PROJECTS

• RELAPLAMED Network. ALFA Programme, European Union. Universities: Salamanca, Valencia, Génova, Coimbra, Chile, Belo Horizonte, Panamá, Colombia. (1997-2001).
• RELAPLAMED Project. Nº 60275.9. ALFA Programme, European Union. Universities: Genova, Coimbra, Salamanca, Valencia, Nacional de Colombia, Panamá, Chile y Federal de Minas Gerais (1998-2001).
• International coordinator, PIBARTRI Project (natural anti-inflammatory agents), Iberoamerican Programme of Scence and Technology for Development (CYTED), Ministery of Science and Technology..This project has been developed by a hundred researchers from Argentina, Bolivia, Brasil, Chile, Costa Rica, Colombia, Cuba, Méjico, Panamá and Spain (University of Valencia, University of Salamanca, University Complutense de Madrid, University of Barcelona, University of Córdoba, University of Sevilla) (2000-2004).
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• EUROPEAN COMMISSION-RESEARCH DIRECTORATE GENERAL CONTRACT: Marie Curie Host Fellowship contract Nº HPMD-CT-2001-00102.

NATIONAL PROJECTS:

• "Molecular and cellular mechanisms of new agents acting on inflammatory and immune processes" SAF97-0249: C. I. C. Y T. (1997-2000).
• "Design, synthesis and preclinical investigations on new antiinflammatory drugs " Nº Proyect 1FD97-0373-C02-01. FEDER Funds (1999-2001)
• "Preclinical study on cellular and animal models of new molecules from marine and synthetic origin in the inflammatory process" SAF2001-2639. C. I. C. Y T. (2002-2004).
• "Study of the molecular mechanisms involved in the genesis and evolution of chronic arthritis using cellular and animal models" SAF2001-2919. C. I. C. Y T. (2002-2004).
• "Pharmacological study of new molecules from marine origin with antipsoriatic properties which interact with nuclear transcription factors" Nº Proyect G. V.04B-074. Generalitat Valenciana (2004-2005).
• "Experimental models of inflammation in human synoviocytes and chondrocytes" Nº Proyect CTIDIB/2002/213. Generalitat Valenciana (2002-2003).
• Research groups grant (grupos03/201) (2003-2005). Generalitat Valenciana.
• "Synthesis and pharmacological, pharmacokinetic and toxicological study of a new antiinflammatory inhibiting cyclooxygenase-2" PTR1995-0728-OP-02-01: Ministery of Education and Science (2004-2006).
• "Regulatory mechanisms controlling the production of tissue injury in chronic inflammation" SAF2004-03835. Ministery of Education and Science (2005-2008).

A wide range of mechanisms are involved in the production of tissue injury during chronic inflammation, with multiple points allowing regulatory interactions. Previously, we have demonstrated the relevant role that proteins such as heme oxygenase-1 (HO-1) play in the activation and functions of the different cell types driving the inflammatory process. This protein may be regulated by cytokines and in turn, it can affect the production of relevant mediators such as those derived from nitric oxide synthase-2 and cyclo-oxygenase-2 activities. This project was aimed at elucidating the mechanisms involved in the pathogenia of chronic inflammatory conditions, such as rheumatoid arthritis and osteoarthritis, with a focus on HO-1 influence on cellular functions. In addition, we wish to establish the consequences derived from HO-1 modulation on the inflammatory process. Thus, we could contribute to the finding of new targets for the control of conditions with a difficult management and a high cost.

CONTRACTS WITH PHARMACEUTICAL COMPANIES: Grupo Ferrer, Vita-Invest, ASAC, Biobérica, Baxter and Syntrix Biosystems USA.