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Article: Enhanced In Vitro Expression of Filaggrin and Antimicrobial Peptides Following Application of Glycosaminoglycans and a Sphingomyelin-Rich Lipid Extract

Segarra, Sergi / Naiken, Tanesha / Garnier, Julien / Hamon, Valérie / Coussay, Nathalie / Bernard, François-Xavier

Veterinary sciences. 2022 June 27, v. 9, no. 7

2022

Abstract: Filaggrin is an epidermal protein involved in skin barrier formation and hydration, whose expression is altered in canine atopic dermatitis (CAD). CAD patients also present an abnormal immune response with an altered expression of antimicrobial peptides ( ...

Abstract	Filaggrin is an epidermal protein involved in skin barrier formation and hydration, whose expression is altered in canine atopic dermatitis (CAD). CAD patients also present an abnormal immune response with an altered expression of antimicrobial peptides (AMPs), such as β-defensins and cathelicidins. Sphingolipids and glycosaminoglycans (GAGs) have been reported to improve the skin barrier in several animal species, including dogs. Our objective was to evaluate the in vitro effects of a sphingomyelin-rich lipid extract (LE), a hyaluronic acid-rich GAG matrix, and their combination, on the expression of filaggrin and human β-defensin 2 (hBD-2). Filaggrin expression was quantified in a reconstructed human epidermis (RHE), and hBD-2 in normal human epidermal keratinocyte (NHEK) cultures. LE and GAGs were tested at 0.02 mg/mL, with or without adding a cytokine mix. A significant increase in mean hBD-2, compared to the control (99 pg/mL) was achieved with LE (138 pg/mL) and LE+GAGs (165 pg/mL). Filaggrin increased with GAGs (202% ± 83) and LE (193% ± 44) vs. the stimulated control, but this difference was statistically significant (p < 0.05) only with LE+GAGs (210% ± 39). In conclusion, the tested GAGs and LE enhance filaggrin and AMP expression in vitro, which might benefit CAD patients if applied in vivo.
Keywords	artificial skin ; atopic dermatitis ; cathelicidins ; cytokines ; dogs ; glycosaminoglycans ; humans ; immune response ; keratinocytes ; sphingolipids
Language	English
Dates of publication	2022-0627
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2768971-2
ISSN	2306-7381
ISSN	2306-7381
DOI	10.3390/vetsci9070323
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Enhanced In Vitro Expression of Filaggrin and Antimicrobial Peptides Following Application of Glycosaminoglycans and a Sphingomyelin-Rich Lipid Extract.

Segarra, Sergi / Naiken, Tanesha / Garnier, Julien / Hamon, Valérie / Coussay, Nathalie / Bernard, François-Xavier

Veterinary sciences

2022 Volume 9, Issue 7

Abstract	Filaggrin is an epidermal protein involved in skin barrier formation and hydration, whose expression is altered in canine atopic dermatitis (CAD). CAD patients also present an abnormal immune response with an altered expression of antimicrobial peptides (AMPs), such as β-defensins and cathelicidins. Sphingolipids and glycosaminoglycans (GAGs) have been reported to improve the skin barrier in several animal species, including dogs. Our objective was to evaluate the in vitro effects of a sphingomyelin-rich lipid extract (LE), a hyaluronic acid-rich GAG matrix, and their combination, on the expression of filaggrin and human β-defensin 2 (hBD-2). Filaggrin expression was quantified in a reconstructed human epidermis (RHE), and hBD-2 in normal human epidermal keratinocyte (NHEK) cultures. LE and GAGs were tested at 0.02 mg/mL, with or without adding a cytokine mix. A significant increase in mean hBD-2, compared to the control (99 pg/mL) was achieved with LE (138 pg/mL) and LE+GAGs (165 pg/mL). Filaggrin increased with GAGs (202% ± 83) and LE (193% ± 44) vs. the stimulated control, but this difference was statistically significant (p < 0.05) only with LE+GAGs (210% ± 39). In conclusion, the tested GAGs and LE enhance filaggrin and AMP expression in vitro, which might benefit CAD patients if applied in vivo.
Language	English
Publishing date	2022-06-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2768971-2
ISSN	2306-7381 ; 2306-7381
ISSN (online)	2306-7381
ISSN	2306-7381
DOI	10.3390/vetsci9070323
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Antiviral Effect of hBD-3 and LL-37 during Human Primary Keratinocyte Infection with West Nile Virus

Chessa, Céline / Bodet, Charles / Jousselin, Clément / Larivière, Andy / Damour, Alexia / Garnier, Julien / Lévêque, Nicolas / Garcia, Magali

Viruses. 2022 July 15, v. 14, no. 7

2022

Abstract: West Nile virus (WNV) is an emerging flavivirus transmitted through mosquito bites and responsible for a wide range of clinical manifestations. Following their inoculation within the skin, flaviviruses replicate in keratinocytes of the epidermis, ... ...

Abstract	West Nile virus (WNV) is an emerging flavivirus transmitted through mosquito bites and responsible for a wide range of clinical manifestations. Following their inoculation within the skin, flaviviruses replicate in keratinocytes of the epidermis, inducing an innate immune response including the production of antimicrobial peptides (AMPs). Among them, the cathelicidin LL-37 and the human beta-defensin (hBD)-3 are known for their antimicrobial and immunomodulatory properties. We assessed their role during WNV infection of human primary keratinocytes. LL-37 reduced the viral load in the supernatant of infected keratinocytes and of the titer of a viral inoculum incubated in the presence of the peptide, suggesting a direct antiviral effect of this AMP. Conversely, WNV replication was not inhibited by hBD-3. The two peptides then demonstrated immunomodulatory properties whether in the context of keratinocyte stimulation by poly(I:C) or infection by WNV, but not alone. This study demonstrates the immunostimulatory properties of these two skin AMPs at the initial site of WNV replication and the ability of LL-37 to directly inactivate West Nile viral infectious particles. The results provide new information on the multiple functions of these two peptides and underline the potential of AMPs as new antiviral strategies in the fight against flaviviral infections.
Keywords	Culicidae ; West Nile virus ; antiviral properties ; cathelicidins ; humans ; immunostimulants ; innate immunity ; inoculum ; keratinocytes ; viral load
Language	English
Dates of publication	2022-0715
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14071552
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Antiviral Effect of hBD-3 and LL-37 during Human Primary Keratinocyte Infection with West Nile Virus.

Chessa, Céline / Bodet, Charles / Jousselin, Clément / Larivière, Andy / Damour, Alexia / Garnier, Julien / Lévêque, Nicolas / Garcia, Magali

Viruses

2022 Volume 14, Issue 7

Abstract	West Nile virus (WNV) is an emerging flavivirus transmitted through mosquito bites and responsible for a wide range of clinical manifestations. Following their inoculation within the skin, flaviviruses replicate in keratinocytes of the epidermis, inducing an innate immune response including the production of antimicrobial peptides (AMPs). Among them, the cathelicidin LL-37 and the human beta-defensin (hBD)-3 are known for their antimicrobial and immunomodulatory properties. We assessed their role during WNV infection of human primary keratinocytes. LL-37 reduced the viral load in the supernatant of infected keratinocytes and of the titer of a viral inoculum incubated in the presence of the peptide, suggesting a direct antiviral effect of this AMP. Conversely, WNV replication was not inhibited by hBD-3. The two peptides then demonstrated immunomodulatory properties whether in the context of keratinocyte stimulation by poly(I:C) or infection by WNV, but not alone. This study demonstrates the immunostimulatory properties of these two skin AMPs at the initial site of WNV replication and the ability of LL-37 to directly inactivate West Nile viral infectious particles. The results provide new information on the multiple functions of these two peptides and underline the potential of AMPs as new antiviral strategies in the fight against flaviviral infections.
MeSH term(s)	Antiviral Restriction Factors/immunology ; Cathelicidins/immunology ; Humans ; Keratinocytes/virology ; West Nile Fever/immunology ; West Nile virus ; beta-Defensins/immunology
Chemical Substances	Antiviral Restriction Factors ; CAMP protein, human ; Cathelicidins ; beta-Defensins
Language	English
Publishing date	2022-07-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14071552
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Adolescent obesity incurs adult skeletal deficits in murine induced obesity model.

Ben Tahar, Soha / Garnier, Julien / Eller, Kerry / DiMauro, Nicole / Piet, Judith / Mehta, Shihkar / Bajpayee, Ambika G / Shefelbine, Sandra J

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

2022 Volume 41, Issue 2, Page(s) 386–395

Abstract: Adolescent obesity has risen dramatically in the last few decades. While adult obesity may be osteoprotective, the effects of obesity during adolescence, which is a period of massive bone accrual, are not clear. We used a murine model of induced ... ...

Abstract	Adolescent obesity has risen dramatically in the last few decades. While adult obesity may be osteoprotective, the effects of obesity during adolescence, which is a period of massive bone accrual, are not clear. We used a murine model of induced adolescent obesity to examine the structural, mechanical, and compositional differences between obese and healthy weight bone in 16-week-old female C57Bl6 mice. We also examined the effects of a return to normal weight after skeletal maturity (24 weeks old). We found obese adolescent bone exhibited decreased trabecular bone volume, increased cortical diameter, increased ultimate stress, and increased brittleness (decreased plastic energy to fracture), similar to an aging phenotype. The trabecular bone deficits remained after return to normal weight after skeletal maturity. However, after returning to normal diet, there was no difference in ultimate stress nor plastic energy to fracture between groups as the normal diet group increased ultimate stress and brittleness. Interestingly, compositional changes appeared in the former high-fat diet mice after skeletal maturity with a lower mineral to matrix ratio compared to normal diet mice. In addition there was a trend toward increased fluorescent advanced glycation endproducts in the former high-fat diet mice compared to normal diet mice but this did not reach significance (p < 0.05) due to the large variability. The skeletal consequences of adolescent obesity may have lasting implications for the adult skeleton even after return to normal weight. Given the rates of adolescent obesity, skeletal health should be a concern.
MeSH term(s)	Animals ; Female ; Mice ; Pediatric Obesity ; Mice, Inbred C57BL ; Bone and Bones ; Cancellous Bone ; Diet, High-Fat/adverse effects ; Fractures, Bone ; Bone Density
Language	English
Publishing date	2022-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605542-4
ISSN	1554-527X ; 0736-0266
ISSN (online)	1554-527X
ISSN	0736-0266
DOI	10.1002/jor.25378
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Online: UK in or UK out?

Garnier, Julien

A common cycle analysis between the UK and the Euro zone

(Document de travail / Centre d'Etudes Prospectives et d'Informations Internationales ; 2004,17)

2004

Author's details	Julien Garnier
Series title	Document de travail / Centre d'Etudes Prospectives et d'Informations Internationales ; 2004,17
Keywords	Konjunkturzusammenhang ; Optimaler Währungsraum ; Schätzung ; Großbritannien ; EU-Staaten
Language	English
Size	Online-Ressource, 44 p., text, ill
Publisher	CEPII
Publishing place	Paris
Document type	Book ; Online
Note	IMD-Felder maschinell generiert ; Zsfassung in franz. Sprache
Database	ECONomics Information System

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Article ; Online: Mechanoadaptation of the bones of mice with high fat diet induced obesity in response to cyclical loading.

Eller, Kerry / DiMauro, Nicole / Garnier, Julien / Ruberti, Anika / Meslier, Quentin / Piet, Judith / Shefelbine, Sandra J

Journal of biomechanics

2021 Volume 124, Page(s) 110569

Abstract: An upward trend in childhood obesity implies a great need to determine its effects, both immediate and long-term. Obesity is osteoprotective in adults, but we know very little about the effects of obesity on the growing skeleton, particularly its ability ...

Abstract	An upward trend in childhood obesity implies a great need to determine its effects, both immediate and long-term. Obesity is osteoprotective in adults, but we know very little about the effects of obesity on the growing skeleton, particularly its ability to adapt to load. The objective of this research is to assess bone mechanoadaptation in adolescent obese mice. Ten mice were fed a high-fat diet (HFD) from 4 to 16 weeks of age, while a control group of the same size received a normal diet (ND). At 14 weeks of age, right tibiae were cyclically loaded with a 12 N peak load for HFD mice and a 9 N peak load for ND mice three times a week for two weeks, resulting in equal peak strains of about 2500 microstrain. At 16 weeks of age, mice were sacrificed, and tibiae and gonadal fat pads were dissected. Fat pads were weighed as an obesity indicator, and tibiae were imaged with microCT to measure bone structure. The left tibiae (nonloaded) were subsequently decalcified, stained with osmium, and scanned to quantify marrow fat. Results showed that HFD mice had larger tibial cross-sectional areas compared to ND mice, as well as greater marrow adiposity. However, there was no significant difference in the amount of bone adaptation in the cortical or trabecular bone between the two groups. This indicates that the bones of HFD and ND mice adapt equally well to loading.
MeSH term(s)	Adipose Tissue ; Animals ; Bone and Bones ; Diet, High-Fat/adverse effects ; Mice ; Mice, Inbred C57BL ; Pediatric Obesity ; Tibia/diagnostic imaging
Language	English
Publishing date	2021-06-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218076-5
ISSN	1873-2380 ; 0021-9290
ISSN (online)	1873-2380
ISSN	0021-9290
DOI	10.1016/j.jbiomech.2021.110569
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Online: Has the similarity of business cycles in Europe increased with the monetary integration process?

Garnier, Julien

A use of the classical business cycles

(EUI working paper / ECO ; 2003,12)

2003

Institution	European University Institute / Department of Economics
Author's details	Julien Garnier
Series title	EUI working paper / ECO ; 2003,12
Keywords	Konjunkturtheorie ; Konjunkturzusammenhang ; Währungsunion ; EU-Staaten
Language	English
Size	Online-Ressource, 43 p., text, Ill
Edition	[Elektronische Ressource]
Publishing place	Badia Fiesolana, San Domenico (Fl)
Document type	Book ; Online
Note	IMD-Felder maschinell generiert
Database	ECONomics Information System

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Article ; Online: Dermal fibroblasts are the key sensors of aseptic skin inflammation through interleukin 1 release by lesioned keratinocytes.

Cordier-Dirikoc, Sevda / Pedretti, Nathalie / Garnier, Julien / Clarhaut-Charreau, Sandrine / Ryffel, Bernhard / Morel, Franck / Bernard, François-Xavier / Hamon de Almeida, Valérie / Lecron, Jean-Claude / Jégou, Jean-François

Frontiers in immunology

2022 Volume 13, Page(s) 984045

Abstract: IL-1 plays a crucial role in triggering sterile inflammation following tissue injury. Although most studies associate IL-1 release by injured cells to the recruitment of neutrophils for tissue repair, the inflammatory cascade involves several molecular ... ...

Abstract	IL-1 plays a crucial role in triggering sterile inflammation following tissue injury. Although most studies associate IL-1 release by injured cells to the recruitment of neutrophils for tissue repair, the inflammatory cascade involves several molecular and cellular actors whose role remains to be specified. In the present study, we identified dermal fibroblasts among the IL-1R1-expressing skin cells as key sensors of IL-1 released by injured keratinocytes. After
MeSH term(s)	Mice ; Animals ; Interleukin-1/metabolism ; Interleukin 1 Receptor Antagonist Protein/metabolism ; Interleukin-8/metabolism ; Endothelial Cells/metabolism ; Cells, Cultured ; Keratinocytes/metabolism ; Dermatitis/metabolism ; Fibroblasts/metabolism ; Inflammation/metabolism
Chemical Substances	Interleukin-1 ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-8
Language	English
Publishing date	2022-10-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.984045
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: 3D visualization of macromolecule synthesis.

Duerr, Timothy J / Comellas, Ester / Jeon, Eun Kyung / Farkas, Johanna E / Joetzjer, Marylou / Garnier, Julien / Shefelbine, Sandra J / Monaghan, James R

eLife

2020 Volume 9

Abstract: Measuring nascent macromolecular synthesis in vivo is key to understanding how cells and tissues progress through development and respond to external cues. Here we perform in vivo injection of alkyne- or azide-modified analogs of thymidine, uridine, ... ...

Abstract	Measuring nascent macromolecular synthesis in vivo is key to understanding how cells and tissues progress through development and respond to external cues. Here we perform in vivo injection of alkyne- or azide-modified analogs of thymidine, uridine, methionine, and glucosamine to label nascent synthesis of DNA, RNA, protein, and glycosylation. Three-dimensional volumetric imaging of nascent macromolecule synthesis was performed in axolotl salamander tissue using whole-mount click chemistry-based fluorescent staining followed by light sheet fluorescent microscopy. We also developed an image processing pipeline for segmentation and classification of morphological regions of interest and individual cells, and we apply this pipeline to the regenerating humerus. We demonstrate our approach is sensitive to biological perturbations by measuring changes in DNA synthesis after limb denervation. This method provides a powerful means to quantitatively interrogate macromolecule synthesis in heterogenous tissues at the organ, cellular, and molecular levels of organization.
MeSH term(s)	Ambystoma mexicanum ; Animals ; Bone Regeneration ; Click Chemistry ; Image Processing, Computer-Assisted ; Macromolecular Substances/chemical synthesis ; Nucleic Acids/chemical synthesis ; Proteins/chemical synthesis ; Tissue Culture Techniques
Chemical Substances	Macromolecular Substances ; Nucleic Acids ; Proteins
Language	English
Publishing date	2020-10-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.60354
Database	MEDical Literature Analysis and Retrieval System OnLINE

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