Sex Hormone–Dependent Lipid Mediator Formation in Male and Female Mice During Peritonitis
Introduction: Sex differences in inflammation are obvious and contribute to divergences in the incidence and severity of inflammation-related diseases that frequently preponderate in women. Lipid mediators (LMs), mainly produced by lipoxygenase (LOX) and cyclooxygenase (COX) pathways from polyunsatu...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.818544/full |
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| author | Fabiana Troisi Simona Pace Paul M. Jordan Katharina P. L. Meyer Rossella Bilancia Armando Ialenti Francesca Borrelli Antonietta Rossi Lidia Sautebin Charles N. Serhan Oliver Werz |
| author_facet | Fabiana Troisi Simona Pace Paul M. Jordan Katharina P. L. Meyer Rossella Bilancia Armando Ialenti Francesca Borrelli Antonietta Rossi Lidia Sautebin Charles N. Serhan Oliver Werz |
| author_sort | Fabiana Troisi |
| collection | DOAJ |
| description | Introduction: Sex differences in inflammation are obvious and contribute to divergences in the incidence and severity of inflammation-related diseases that frequently preponderate in women. Lipid mediators (LMs), mainly produced by lipoxygenase (LOX) and cyclooxygenase (COX) pathways from polyunsaturated fatty acids (PUFAs), regulate all stages of inflammation. Experimental and clinical studies revealed sex divergences for selected LM pathways without covering the entire LM spectrum, and only few studies have addressed the respective role of sex hormones. Here, we performed the comprehensive LM profile analysis with inflammatory peritoneal exudates and plasma from male and female mice in zymosan-induced peritonitis to identify the potential sex differences in LM biosynthesis during the inflammatory response. We also addressed the impact of sex hormones by employing gonadectomy.Methods: Adult male and female CD1 mice received intraperitoneal injection of zymosan to induce peritonitis, a well-established experimental model of acute, self-resolving inflammation. Mice were gonadectomized 5 weeks prior to peritonitis induction. Peritoneal exudates and plasma were taken at 4 (peak of inflammation) and 24 h (onset of resolution) post zymosan and subjected to UPLC–MS-MS–based LM signature profiling; exudates were analyzed for LM biosynthetic proteins by Western blot; and plasma was analyzed for cytokines by ELISA.Results: Pro-inflammatory COX and 5-LOX products predominated in the peritoneum of males at 4 and 24 h post-zymosan, respectively, with slightly higher 12/15-LOX products in males after 24 h. Amounts of COX-2, 5-LOX/FLAP, and 15-LOX-1 were similar in exudates of males and females. In plasma of males, only moderate elevation of these LMs was apparent. At 4 h post-zymosan, gonadectomy strongly elevated 12/15-LOX products in the exudates of males, while in females, free PUFA and LOX products were rather impaired. In plasma, gonadectomy impaired most LMs in both sexes at 4 h with rather up-regulatory effects at 24 h. Finally, elevated 15-LOX-1 protein was evident in exudates of males at 24 h which was impaired by orchiectomy without the striking impact of gonadectomy on other enzymes in both sexes.Conclusions: Our results reveal obvious sex differences and roles of sex hormones in LM biosynthetic networks in acute self-resolving inflammation in mice, with several preponderances in males that appear under the control of androgens. |
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| language | English |
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| spelling | doaj.art-d298ead92d6e41e2b58e7b5c8604f3e22022-12-21T21:28:24ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-01-011210.3389/fphar.2021.818544818544Sex Hormone–Dependent Lipid Mediator Formation in Male and Female Mice During PeritonitisFabiana Troisi0Simona Pace1Paul M. Jordan2Katharina P. L. Meyer3Rossella Bilancia4Armando Ialenti5Francesca Borrelli6Antonietta Rossi7Lidia Sautebin8Charles N. Serhan9Oliver Werz10Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Jena, GermanyDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Jena, GermanyDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Jena, GermanyDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Jena, GermanyDepartment of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, ItalyCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States of AmericaDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Jena, GermanyIntroduction: Sex differences in inflammation are obvious and contribute to divergences in the incidence and severity of inflammation-related diseases that frequently preponderate in women. Lipid mediators (LMs), mainly produced by lipoxygenase (LOX) and cyclooxygenase (COX) pathways from polyunsaturated fatty acids (PUFAs), regulate all stages of inflammation. Experimental and clinical studies revealed sex divergences for selected LM pathways without covering the entire LM spectrum, and only few studies have addressed the respective role of sex hormones. Here, we performed the comprehensive LM profile analysis with inflammatory peritoneal exudates and plasma from male and female mice in zymosan-induced peritonitis to identify the potential sex differences in LM biosynthesis during the inflammatory response. We also addressed the impact of sex hormones by employing gonadectomy.Methods: Adult male and female CD1 mice received intraperitoneal injection of zymosan to induce peritonitis, a well-established experimental model of acute, self-resolving inflammation. Mice were gonadectomized 5 weeks prior to peritonitis induction. Peritoneal exudates and plasma were taken at 4 (peak of inflammation) and 24 h (onset of resolution) post zymosan and subjected to UPLC–MS-MS–based LM signature profiling; exudates were analyzed for LM biosynthetic proteins by Western blot; and plasma was analyzed for cytokines by ELISA.Results: Pro-inflammatory COX and 5-LOX products predominated in the peritoneum of males at 4 and 24 h post-zymosan, respectively, with slightly higher 12/15-LOX products in males after 24 h. Amounts of COX-2, 5-LOX/FLAP, and 15-LOX-1 were similar in exudates of males and females. In plasma of males, only moderate elevation of these LMs was apparent. At 4 h post-zymosan, gonadectomy strongly elevated 12/15-LOX products in the exudates of males, while in females, free PUFA and LOX products were rather impaired. In plasma, gonadectomy impaired most LMs in both sexes at 4 h with rather up-regulatory effects at 24 h. Finally, elevated 15-LOX-1 protein was evident in exudates of males at 24 h which was impaired by orchiectomy without the striking impact of gonadectomy on other enzymes in both sexes.Conclusions: Our results reveal obvious sex differences and roles of sex hormones in LM biosynthetic networks in acute self-resolving inflammation in mice, with several preponderances in males that appear under the control of androgens.https://www.frontiersin.org/articles/10.3389/fphar.2021.818544/fullsex differenceslipoxygenaselipid mediatorspecialized pro-resolving mediatorsperitonitisinflammation |
| spellingShingle | Fabiana Troisi Simona Pace Paul M. Jordan Katharina P. L. Meyer Rossella Bilancia Armando Ialenti Francesca Borrelli Antonietta Rossi Lidia Sautebin Charles N. Serhan Oliver Werz Sex Hormone–Dependent Lipid Mediator Formation in Male and Female Mice During Peritonitis Frontiers in Pharmacology sex differences lipoxygenase lipid mediator specialized pro-resolving mediators peritonitis inflammation |
| title | Sex Hormone–Dependent Lipid Mediator Formation in Male and Female Mice During Peritonitis |
| title_full | Sex Hormone–Dependent Lipid Mediator Formation in Male and Female Mice During Peritonitis |
| title_fullStr | Sex Hormone–Dependent Lipid Mediator Formation in Male and Female Mice During Peritonitis |
| title_full_unstemmed | Sex Hormone–Dependent Lipid Mediator Formation in Male and Female Mice During Peritonitis |
| title_short | Sex Hormone–Dependent Lipid Mediator Formation in Male and Female Mice During Peritonitis |
| title_sort | sex hormone dependent lipid mediator formation in male and female mice during peritonitis |
| topic | sex differences lipoxygenase lipid mediator specialized pro-resolving mediators peritonitis inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.818544/full |
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