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Article: Effects of Sex Steroids on Fish Leukocytes.

Chaves-Pozo, Elena / García-Ayala, Alfonsa / Cabas, Isabel

2018 Volume 7, Issue 1

Abstract: In vertebrates, in addition to their classically reproductive functions, steroids regulate the immune system. This action is possible mainly due to the presence of steroid receptors in the different immune cell types. Much evidence suggests that the ... ...

Abstract	In vertebrates, in addition to their classically reproductive functions, steroids regulate the immune system. This action is possible mainly due to the presence of steroid receptors in the different immune cell types. Much evidence suggests that the immune system of fish is vulnerable to xenosteroids, which are ubiquitous in the aquatic environment. In vivo and in vitro assays have amply demonstrated that oestrogens interfere with both the innate and the adaptive immune system of fish by regulating the main leukocyte activities and transcriptional genes. They activate nuclear oestrogen receptors and/or G-protein coupled oestrogen receptor. Less understood is the role of androgens in the immune system, mainly due to the complexity of the transcriptional regulation of androgen receptors in fish. The aim of this manuscript is to review our present knowledge concerning the effect of sex steroid hormones and the presence of their receptors on fish leukocytes, taking into consideration that the studies performed vary as regard the fish species, doses, exposure protocols and hormones used. Moreover, we also include evidence of the probable role of progestins in the regulation of the immune system of fish.
Language	English
Publishing date	2018-01-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology7010009
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Peroxisome proliferator-activated receptors alpha and beta mediate the anti-inflammatory effects of the cyclopentenone prostaglandin 15-deoxy-Δ

Gómez-Abellán, Victoria / Pérez-Oliva, Ana B / Cabas, Isabel / Hermi, Fatma / Arizcun, Marta / García-Moreno, Diana / Sepulcre, María P / Mulero, Victoriano

Developmental and comparative immunology

2022 Volume 136, Page(s) 104498

Abstract: Prostaglandins (PGs) are highly reactive small lipophilic molecules derived from polyunsaturated fatty acids of the cell membrane and play a key role in the resolution of inflammation processes. 15-deoxy- ... ...

Abstract	Prostaglandins (PGs) are highly reactive small lipophilic molecules derived from polyunsaturated fatty acids of the cell membrane and play a key role in the resolution of inflammation processes. 15-deoxy-Δ
MeSH term(s)	Animals ; Cyclooxygenase 2/metabolism ; Cyclopentanes ; DNA, Bacterial ; Granulocytes/metabolism ; Inflammation ; Mammals ; PPAR alpha ; PPAR gamma/genetics ; PPAR gamma/metabolism ; PPAR-beta ; Prostaglandin D2/chemistry ; Prostaglandin D2/pharmacology ; Prostaglandins ; Reactive Oxygen Species ; Sea Bream/metabolism
Chemical Substances	Cyclopentanes ; DNA, Bacterial ; PPAR alpha ; PPAR gamma ; PPAR-beta ; Prostaglandins ; Reactive Oxygen Species ; Cyclooxygenase 2 (EC 1.14.99.1) ; cyclopentenone (Q0U2IGF9CK) ; Prostaglandin D2 (RXY07S6CZ2)
Language	English
Publishing date	2022-08-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2022.104498
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Peroxisome proliferator-activated receptors alpha and beta mediate the anti-inflammatory effects of the cyclopentenone prostaglandin 15-deoxy-Δ12,14-PGJ2 in fish granulocytes

Gómez-Abellán, Victoria / Pérez-Oliva, Ana B. / Cabas, Isabel / Hermi, Fatma / Arizcun, Marta / García-Moreno, Diana / Sepulcre, María P. / Mulero, Victoriano

Developmental and comparative immunology. 2022 Nov., v. 136

2022

Abstract	Prostaglandins (PGs) are highly reactive small lipophilic molecules derived from polyunsaturated fatty acids of the cell membrane and play a key role in the resolution of inflammation processes. 15-deoxy-Δ¹²,¹⁴-PGJ₂ (15dPGJ₂) is a cyclopentenone PG (CyPG) of the J series with anti-inflammatory, anti-proliferative and pro-apoptotic effects. This CyPG can signal through: (i) the PGD₂ receptor (DP2) and peroxisome proliferator-activated receptor γ (PPARγ) or (ii) by covalent binding to protein nucleophiles, such as, thiols groups of cysteine, lysine or histidine via a Michael addition reaction, modifying its structure and function. In this work we show that acidophilic granulocytes (AGs) of gilthead seabream (Sparus aurata L.), the functional equivalent to mammalian neutrophils, constitutively expressed ppara, pparb and pparg genes, the latter showing the highest expression and up-regulation when stimulated by bacterial DNA. In addition, we tested the ability of 15dPGJ₂, and its biotinylated analog, as well as several PPARγ ligands, to modulate reactive oxygen species (ROS) and/or cytokines production during a Toll like receptor (TLR)-mediated granulocyte response. Thus, 15dPGJ₂ was able to significantly decrease bacterial DNA-induced ROS production and transcript levels of pparg, interleukin-1β (il1b) and prostaglandin-endoperoxide synthase 2 (ptgs2). In contrast, its biotinylated analog was less potent and a higher dose was required to elicit the same effects on ROS production and cytokine expression. In addition, different PPARγ agonists were able to mimic the effects of 15dPGJ₂. Conversely, the PPARγ antagonist T007097 abolished the effect of 15dPGJ₂ on DNA bacterial-induced ROS production. Surprisingly, transactivation assays revealed that both 15dPGJ₂ and its biotinylated analog signaled via Pparα and Pparβ, but not by Pparγ. These results were further confirmed by HPLC/MS analysis, where Pparβ was identified as an interactor of biotin-15dPGJ₂ in naïve and DNA-stimulated leukocytes. Taken together, our data show that 15dPGJ₂ acts both through Ppar activation and covalent binding to proteins in fish granulocytes and identify for the first time in vertebrates a role for Pparα and Pparβ in the resolution of inflammation mediated by 15dPGJ₂.
Keywords	DNA ; Lewis bases ; Sparus aurata ; antagonists ; apoptosis ; cell membranes ; chemical reactions ; cysteine ; fish ; histidine ; inflammation ; ligands ; lipophilicity ; lysine ; mammals ; neutrophils ; prostaglandin synthase ; prostaglandins ; reactive oxygen species ; thiols ; transcriptional activation
Language	English
Dates of publication	2022-11
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2022.104498
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Evolution of LPS recognition and signaling: The bony fish perspective.

Martínez-López, Alicia / Tyrkalska, Sylwia D / Alcaraz-Pérez, Francisca / Cabas, Isabel / Candel, Sergio / Martínez Morcillo, Francisco J / Sepulcre, María P / García-Moreno, Diana / Cayuela, María L / Mulero, Victoriano

Developmental and comparative immunology

2023 Volume 145, Page(s) 104710

Abstract: Fish are the most diverse and successful group of vertebrate animals, with about 30,000 species. The study of fish immunity is of great importance for understanding the evolution of vertebrate immunity, as they are the first animals to show both innate ... ...

Abstract	Fish are the most diverse and successful group of vertebrate animals, with about 30,000 species. The study of fish immunity is of great importance for understanding the evolution of vertebrate immunity, as they are the first animals to show both innate and adaptive immune responses. Although fish immunity is similar to that of mammals, there are obvious differences, such as their dependence of ambient temperature, their poor antibody response, and lack of antibody switching and lymph nodes. In addition, several important differences have also been found between the innate immune responses of fish and mammals. Among these, we will discuss in this review the high resistance of fish to the toxic effects of lipopolysaccharide (LPS) which can be explained by the absence of a Toll-like receptor 4 (Tlr4) ortholog in most fish species or by the inability of the Tlr4/Md2 (Myeloid differentiation 2) complex to recognize LPS, together with the presence of a negative regulator of the LPS signaling complex formed by the TLR-like molecule Rp105 (Radioprotective 105) and Md1. Taken together, these data support the idea that, although TLR4 and RP105 arose from a common ancestor to fish and tetrapods, the TLR4/MD2 receptor complex for LPS recognition arose after their divergence about 450 million years ago.
MeSH term(s)	Animals ; Lipopolysaccharides ; Toll-Like Receptor 4/metabolism ; Signal Transduction ; Fishes ; Immunity, Innate ; Lymphocyte Antigen 96 ; Mammals
Chemical Substances	Lipopolysaccharides ; Toll-Like Receptor 4 ; Lymphocyte Antigen 96
Language	English
Publishing date	2023-04-18
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2023.104710
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Article ; Online: NAMPT and PARylation Are Involved in the Pathogenesis of Atopic Dermatitis.

Arroyo, Ana B / Bernal-Carrión, Martín / Cantón-Sandoval, Joaquín / Cabas, Isabel / Corbalán-Vélez, Raúl / Martínez-Menchón, Teresa / Ferri, Belén / Cayuela, María L / García-Moreno, Diana / Mulero, Victoriano

International journal of molecular sciences

2023 Volume 24, Issue 9

Abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease of very high prevalence, especially in childhood, with no specific treatment or cure. As its pathogenesis is complex, multifactorial and not fully understood, further research is needed to ... ...

Abstract	Atopic dermatitis (AD) is a chronic inflammatory skin disease of very high prevalence, especially in childhood, with no specific treatment or cure. As its pathogenesis is complex, multifactorial and not fully understood, further research is needed to increase knowledge and develop new targeted therapies. We have recently demonstrated the critical role of NAD
MeSH term(s)	Animals ; Humans ; Dermatitis, Atopic ; Inflammation ; NAD/metabolism ; Poly (ADP-Ribose) Polymerase-1/metabolism ; Poly Adenosine Diphosphate Ribose/metabolism ; Poly ADP Ribosylation ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Psoriasis/etiology ; Zebrafish/metabolism
Chemical Substances	NAD (0U46U6E8UK) ; Poly (ADP-Ribose) Polymerase-1 (EC 2.4.2.30) ; Poly Adenosine Diphosphate Ribose (26656-46-2) ; Poly(ADP-ribose) Polymerase Inhibitors ; nicotinamide phosphoribosyltransferase, human (EC 2.4.2.12)
Language	English
Publishing date	2023-04-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24097992
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Article ; Online: Evolution of LPS recognition and signaling: The bony fish perspective

Martínez-López, Alicia / Tyrkalska, Sylwia D. / Alcaraz-Pérez, Francisca / Cabas, Isabel / Candel, Sergio / Martínez Morcillo, Francisco J. / Sepulcre, María P. / García-Moreno, Diana / Cayuela, María L. / Mulero, Victoriano

Developmental and Comparative Immunology. 2023 Aug., v. 145 p.104710-

2023

Abstract	Fish are the most diverse and successful group of vertebrate animals, with about 30,000 species. The study of fish immunity is of great importance for understanding the evolution of vertebrate immunity, as they are the first animals to show both innate and adaptive immune responses. Although fish immunity is similar to that of mammals, there are obvious differences, such as their dependence of ambient temperature, their poor antibody response, and lack of antibody switching and lymph nodes. In addition, several important differences have also been found between the innate immune responses of fish and mammals. Among these, we will discuss in this review the high resistance of fish to the toxic effects of lipopolysaccharide (LPS) which can be explained by the absence of a Toll-like receptor 4 (Tlr4) ortholog in most fish species or by the inability of the Tlr4/Md2 (Myeloid differentiation 2) complex to recognize LPS, together with the presence of a negative regulator of the LPS signaling complex formed by the TLR-like molecule Rp105 (Radioprotective 105) and Md1. Taken together, these data support the idea that, although TLR4 and RP105 arose from a common ancestor to fish and tetrapods, the TLR4/MD2 receptor complex for LPS recognition arose after their divergence about 450 million years ago.
Keywords	Toll-like receptor 4 ; ambient temperature ; ancestry ; antibodies ; antibody formation ; evolution ; fish ; lipopolysaccharides ; lymph ; toxicity ; TLR4 ; RP105 ; MD2 ; MD1 ; LPS ; Innate immunity ; Inflammation ; Zebrafish
Language	English
Dates of publication	2023-08
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Use and reproduction
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2023.104710
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Role of estrogens in fish immunity with special emphasis on GPER1.

Cabas, Isabel / Chaves-Pozo, Elena / Mulero, Victoriano / García-Ayala, Alfonsa

Developmental and comparative immunology

2018 Volume 89, Page(s) 102–110

Abstract: It is well accepted that estrogens, the primary female sex hormones, play a key role in modulating different aspects of the immune response. Moreover, estrogens have been linked with the sexual dimorphism observed in some immune disorders, such as ... ...

Abstract	It is well accepted that estrogens, the primary female sex hormones, play a key role in modulating different aspects of the immune response. Moreover, estrogens have been linked with the sexual dimorphism observed in some immune disorders, such as chronic inflammatory and autoimmune diseases. Nevertheless, their effects are often controversial and depend on several factors, such as the pool of estrogen receptors (ERs) involved in the response. Their classical mode of action is through nuclear ERs, which act as transcription factors, promoting the regulation of target genes. However, it has long been noted that some of the estrogen-mediated effects cannot be explained by these classical receptors, since they are rapid and mediated by non-genomic signaling pathways. Hence, the interest in membrane ERs, especially in G protein-coupled estrogen receptor 1 (GPER1), has grown in recent years. Although the presence of nuclear ERs, and ER signaling, in immune cells in mammals and fish has been well documented, information on membrane ERs is much scarcer. In this context, the present manuscript aims to review our knowledge concerning the effect of estrogens on fish immunity, with special emphasis on GPER1. For example, the numerous tools developed over recent years allowed us to report for the first time that the regulation of fish granulocyte functions by estrogens through GPER1 predates the split of fish and tetrapods more than 450 million years ago, pointing to the relevance of estrogens as modulators of the immune responses, and the pivotal role of GPER1 in immunity.
MeSH term(s)	Adaptive Immunity ; Animals ; Estrogens/immunology ; Female ; Fish Proteins/immunology ; Fishes/immunology ; Immunity, Innate ; Immunomodulation ; Leukocytes/immunology ; Male ; Receptors, Estrogen/immunology ; Receptors, G-Protein-Coupled/immunology ; Signal Transduction/immunology
Chemical Substances	Estrogens ; Fish Proteins ; Receptors, Estrogen ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2018-08-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2018.08.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

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ab Jg. 2022: Lesesaal (EG)

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Article: Effects of Sex Steroids on Fish Leukocytes

Chaves-Pozo, Elena / García-Ayala, Alfonsa / Cabas, Isabel

Biology. 2018 Jan. 09, v. 7, no. 1

2018

Abstract	In vertebrates, in addition to their classically reproductive functions, steroids regulate the immune system. This action is possible mainly due to the presence of steroid receptors in the different immune cell types. Much evidence suggests that the immune system of fish is vulnerable to xenosteroids, which are ubiquitous in the aquatic environment. In vivo and in vitro assays have amply demonstrated that oestrogens interfere with both the innate and the adaptive immune system of fish by regulating the main leukocyte activities and transcriptional genes. They activate nuclear oestrogen receptors and/or G-protein coupled oestrogen receptor. Less understood is the role of androgens in the immune system, mainly due to the complexity of the transcriptional regulation of androgen receptors in fish. The aim of this manuscript is to review our present knowledge concerning the effect of sex steroid hormones and the presence of their receptors on fish leukocytes, taking into consideration that the studies performed vary as regard the fish species, doses, exposure protocols and hormones used. Moreover, we also include evidence of the probable role of progestins in the regulation of the immune system of fish.
Keywords	G-proteins ; adaptive immunity ; androgen receptors ; androgens ; aquatic environment ; estrogen receptors ; estrogens ; fish ; genes ; in vitro studies ; leukocytes ; progestational hormones ; steroid hormones ; steroids ; transcription (genetics)
Language	English
Dates of publication	2018-0109
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology7010009
Database	NAL-Catalogue (AGRICOLA)

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Article: Role of estrogens in fish immunity with special emphasis on GPER1

Cabas, Isabel / Alfonsa García-Ayala / Elena Chaves-Pozo / Victoriano Mulero

Developmental and comparative immunology. 2018 Dec., v. 89

2018

Abstract	It is well accepted that estrogens, the primary female sex hormones, play a key role in modulating different aspects of the immune response. Moreover, estrogens have been linked with the sexual dimorphism observed in some immune disorders, such as chronic inflammatory and autoimmune diseases. Nevertheless, their effects are often controversial and depend on several factors, such as the pool of estrogen receptors (ERs) involved in the response. Their classical mode of action is through nuclear ERs, which act as transcription factors, promoting the regulation of target genes. However, it has long been noted that some of the estrogen-mediated effects cannot be explained by these classical receptors, since they are rapid and mediated by non-genomic signaling pathways. Hence, the interest in membrane ERs, especially in G protein-coupled estrogen receptor 1 (GPER1), has grown in recent years. Although the presence of nuclear ERs, and ER signaling, in immune cells in mammals and fish has been well documented, information on membrane ERs is much scarcer. In this context, the present manuscript aims to review our knowledge concerning the effect of estrogens on fish immunity, with special emphasis on GPER1. For example, the numerous tools developed over recent years allowed us to report for the first time that the regulation of fish granulocyte functions by estrogens through GPER1 predates the split of fish and tetrapods more than 450 million years ago, pointing to the relevance of estrogens as modulators of the immune responses, and the pivotal role of GPER1 in immunity.
Keywords	autoimmune diseases ; estrogen receptors ; estrogens ; females ; fish ; immune response ; mammals ; mechanism of action ; sexual dimorphism ; signal transduction
Language	English
Dates of publication	2018-12
Size	p. 102-110.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2018.08.001
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 1327: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: 17α-ethynylestradiol prevents the natural male-to-female sex change in gilthead seabream (Sparus aurata L.).

García Hernández, M Pilar / Cabas, Isabel / Rodenas, M Carmen / Arizcun, Marta / Chaves-Pozo, Elena / Power, Deborah M / García Ayala, Alfonsa

Scientific reports

2020 Volume 10, Issue 1, Page(s) 20067

Abstract: Exposure to 17α-ethynylestradiol ( ... ...

Abstract	Exposure to 17α-ethynylestradiol (EE
MeSH term(s)	Animals ; Estrogens/pharmacology ; Ethinyl Estradiol/pharmacology ; Female ; Fish Proteins/genetics ; Fish Proteins/metabolism ; Gene Expression Regulation ; Liver/drug effects ; Male ; Reproduction ; Sea Bream ; Spermatogenesis ; Testis/drug effects ; Transsexualism/genetics ; Transsexualism/prevention & control ; Vitellogenins/genetics ; Vitellogenins/metabolism
Chemical Substances	Estrogens ; Fish Proteins ; Vitellogenins ; Ethinyl Estradiol (423D2T571U)
Language	English
Publishing date	2020-11-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-76902-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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