Wednesday, 12th December 2018
Cell Biology and Immunology
               Prostanoids actions in inflammatory processes

 

 

 

grupo-400

 


 

 

Miguel Ángel Íñiguez Peña

 ASciStaff

APublications

 

 

 

 

Research summary:

Lipid mediators as prostanoids and cholesterol derivatives play an essential role in inflammatory processes associated to the onset and development of a number of pathologies as cardiovascular diseases. Prostanoids participate in the inflammatory response and exert important actions in the cardiovascular system, modulating vascular homeostasis and participating in the pathogenesis of vascular diseases. Their importance in inflammation and in maintaining cardiovascular homeostasis is highlighted by clinical experience with drugs inhibiting their production as NSAIDs. In spite of their well-known properties as anti-inflammatory drugs, recent studies have shown that cyclooxygenase-2 selective NSAIDs inhibitors increase the risk of adverse cardiovascular side effects. On the other hand, oxysterols and drugs acting as LXR ligands play a central regulatory role in lipid uptake, metabolism and efflux through their properties as transcriptional regulators of gene expression. In addition to their function in lipid metabolism, LXRs have also been found to modulate the immune response and inflammation. These properties have made them particularly attractive targets for intervention in human cardiovascular diseases.

  fig01-300

 

Hypertrophic effect of FP receptor agonists in rat neonatal cardiomyocytes. Cardiomyocytes were treated with prostaglandin (PG) F2α or Fluprostenol (1 μM)and visualized with an antibody antiα-sarcomeric actin revealed with a secondary antibody coupled to Alexa 488 (green). The cell area analysis showed an increase in cell size in the treated cells compared to control.

  ---------------                       

        

  Fig02-300

 

Abdominal aortic aneurysm (AAA) formation in apoE-/- mice infused with Angiotensin II (AngII) or saline as a control. Staining of cross sections taken from the suprarenal region of the aorta shows dilatation and thickening of the abdominal aortic wall and alteration of the elastic laminain mice treated with AngII.

    

 
       

Based on these observations and our previous studies, the main objectives of our line of research include:analysis of the effects of prostanoids and LXR ligands in different cell types as leukocytes and cardiomyocytes, among others; study of the signal transduction pathways mediating hypertrophic effects of prostanoids on cardiomyocytes; and investigation of the contribution of prostanoid –mediated events and LXR ligands to the progression of abdominal aortic aneurysm, by the use of cellular models and an experimental model of this disease in Apo-E null mice and Cox-2 null mice.
Research on the molecular and cellular basis of the actions of prostanoids and LXRs in the cardiovascular pathophysiology is required to clearly understand the benefits and risks of pharmaceutical intervention with COX inhibitors as NSAIDs or synthetic LXR ligands on cardiovascular diseases.


 

Relevant publications:

  • Díaz-Muñoz MD, Osma-García IC, Iñiguez MA, Fresno M. Cyclooxygenase-2 deficiency in macrophages leads to defective p110γ PI3K signaling and impairs cell adhesion and migration. J Immunol. 2013 Jul 1;191(1):395-406. PubMed PMID: 23733875.
  • Díaz-Muñoz MD, Osma-García IC, Fresno M, Iñiguez MA. Involvement of PGE2 and the cAMP signalling pathway in the up-regulation of COX-2 and mPGES-1 expression in LPS-activated macrophages. Biochem J. 2012 Apr 15;443(2):451-61. PubMed PMID: 22268508.
  • Díaz-Muñoz MD, Osma-García IC, Cacheiro-Llaguno C, Fresno M, Iñiguez MA.Coordinated up-regulation of cyclooxygenase-2 and microsomal prostaglandin Esynthase 1 transcription by nuclear factor kappa B and early growth response-1 in macrophages. Cell Signal. 2010 Oct;22(10):1427-36. PubMed PMID: 20546888.
  • Grau R, Punzón C, Fresno M, Iñiguez MA. Peroxisome-proliferator-activatedreceptor alpha agonists inhibit cyclo-oxygenase 2 and vascular endothelial growth factor transcriptional activation in human colorectal carcinoma cells via inhibition of activator protein-1. Biochem J. 2006 Apr 1;395(1):81-8. PubMed PMID: 16343055
  • Duque J, Fresno M, Iñiguez MA. Expression and function of the nuclear factor of activated T cells in colon carcinoma cells: involvement in the regulation of cyclooxygenase-2. J Biol Chem. 2005 Mar 11;280(10):8686-93. PubMed PMID: 15632146.

NOTE! This site uses cookies and similar technologies.

If you not change browser settings, you agree to it. Learn more

I understand

COOKIES POLICY

What are cookies?

A cookie is a file that is downloaded to your computer when you access certain web pages. Cookies allow a web page, among other things, to store and retrieve information about the browsing habits of a user or their equipment and, depending on the information they contain and the way they use their equipment, they can be used to recognize the user.

Types of cookies

Classification of cookies is made according to a series of categories. However, it is necessary to take into account that the same cookie can be included in more than one category.

  1. Cookies according to the entity that manages them

    Depending on the entity that manages the computer or domain from which the cookies are sent and treat the data obtained, we can distinguish:

    • Own cookies: those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which the service requested by the user is provided.
    • Third party cookies: those that are sent to the user's terminal equipment from a computer or domain that is not managed by the publisher, but by another entity that processes the data obtained through the cookies. When cookies are installed from a computer or domain managed by the publisher itself, but the information collected through them is managed by a third party, they cannot be considered as own cookies.

  2. Cookies according to the period of time they remain activated

    Depending on the length of time that they remain activated in the terminal equipment, we can distinguish:

    • Session cookies: type of cookies designed to collect and store data while the user accesses a web page. They are usually used to store information that only is kept to provide the service requested by the user on a single occasion (e.g. a list of products purchased).
    • Persistent cookies: type of cookies in which the data is still stored in the terminal and can be accessed and processed during a period defined by the person responsible for the cookie, which can range from a few minutes to several years.

  3. Cookies according to their purpose

    Depending on the purpose for which the data obtained through cookies are processed, we can distinguish between:

    • Technical cookies: those that allow the user to navigate through a web page, platform or application and the use of different options or services that exist in it, such as controlling traffic and data communication, identifying the session, access to restricted access parts, remember the elements that make up an order, perform the purchase process of an order, make a registration or participation in an event, use security elements during navigation, store content for the broadcast videos or sound or share content through social networks.
    • Personalization cookies: those that allow the user to access the service with some predefined general characteristics based on a series of criteria in the user's terminal, such as the language, the type of browser through which the user accesses the service, the regional configuration from where you access the service, etc.
    • Analytical cookies: those that allow the person responsible for them to monitor and analyse the behaviour of the users of the websites to which they are linked. The information collected through this type of cookies is used in the measurement of the activity of the websites, applications or platforms, and for the elaboration of navigation profiles of the users of said sites, applications and platforms, in order to introduce improvements in the analysis of the data of use made by the users of the service.

Cookies used on our website

The CBMSO website uses Google Analytics. Google Analytics is a simple and easy to use tool that helps website owners to measure how users interact with the content of the site. You can consult more information about the cookies used by Google Analitycs in this link.

Acceptance of the Cookies Policy

The CBMSO assumes that you accept the use of cookies if you continue browsing, considering that it is a conscious and positive action from which the user's consent is inferred. In this regard, you are previously informed that such behaviour will be interpreted that you accept the installation and use of cookies.

Knowing this information, it is possible to carry out the following actions:

How to modify the configuration of cookies

Using your browser you can restrict, block or delete cookies from any web page. In each browser the process is different, here we show you links on this particular of the most used browsers: