The effects of losartan on cytomegalovirus infection in human trabecular meshwork cells.
Actins
/ genetics
Connective Tissue Growth Factor
/ genetics
Cytomegalovirus
/ drug effects
Cytomegalovirus Infections
/ drug therapy
Enzyme-Linked Immunosorbent Assay
Fibrosis
/ drug therapy
Gene Expression Regulation
/ drug effects
Humans
Losartan
/ pharmacology
Protein-Lysine 6-Oxidase
/ genetics
Trabecular Meshwork
/ drug effects
Transforming Growth Factor beta1
/ genetics
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
18
01
2019
accepted:
03
06
2019
entrez:
20
6
2019
pubmed:
20
6
2019
medline:
14
2
2020
Statut:
epublish
Résumé
Human cytomegalovirus (CMV) has been emerged as one of the causes of acute recurrent or chronic hypertensive anterior uveitis in immunocompetent. In hypertensive anterior uveitis, human trabecular meshwork (TM) cells are considered a focus of inflammation. We investigated the effects of losartan, a selective angiotensin II receptor antagonist, on CMV infection in human TM cells. Human TM cells were infected with CMV AD169. Virus infected and mock-infected cells were treated with losartan or dexamethasone or ganciclovir with or without transforming growth factor (TGF)-β1. Viral DNA accumulation and host cell response were analyzed using real-time PCR. Levels of secreted TGF-β1 were measured by determining its concentration in conditioned medium using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kits. CMV infection significantly increased the concentrations of the secreted TGF-β1 at 3, 5, and 7 day post infection in TM cells. Treatment with dexamethasone or losartan significantly decreased the levels of TGF-β1, whereas treatment with ganciclovir did not affect TGF-β1 levels. TM cells treated with TGF-β1 along with the presence of losartan for 48 hours showed marked decrease in the expression of α-smooth muscle actin (SMA), lysyl oxidase (LOX), connective tissue growth factor (CTGF), fibronectin and collagen-1A, compared with cells treated with TGF-β1 alone. CMV-infected TM cells stimulated by TGF-β1 significantly increased the expression of α-SMA and CTGF, which were attenuated by additional treatment with losartan. Losartan inhibited the expression of TGF-β1 and fibrogenic molecules in human TM cells. Thus, losartan has the potential to decrease TM fibrosis in patients with CMV-induced hypertensive anterior uveitis.
Sections du résumé
BACKGROUND
Human cytomegalovirus (CMV) has been emerged as one of the causes of acute recurrent or chronic hypertensive anterior uveitis in immunocompetent. In hypertensive anterior uveitis, human trabecular meshwork (TM) cells are considered a focus of inflammation. We investigated the effects of losartan, a selective angiotensin II receptor antagonist, on CMV infection in human TM cells.
METHODS
Human TM cells were infected with CMV AD169. Virus infected and mock-infected cells were treated with losartan or dexamethasone or ganciclovir with or without transforming growth factor (TGF)-β1. Viral DNA accumulation and host cell response were analyzed using real-time PCR. Levels of secreted TGF-β1 were measured by determining its concentration in conditioned medium using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kits.
RESULTS
CMV infection significantly increased the concentrations of the secreted TGF-β1 at 3, 5, and 7 day post infection in TM cells. Treatment with dexamethasone or losartan significantly decreased the levels of TGF-β1, whereas treatment with ganciclovir did not affect TGF-β1 levels. TM cells treated with TGF-β1 along with the presence of losartan for 48 hours showed marked decrease in the expression of α-smooth muscle actin (SMA), lysyl oxidase (LOX), connective tissue growth factor (CTGF), fibronectin and collagen-1A, compared with cells treated with TGF-β1 alone. CMV-infected TM cells stimulated by TGF-β1 significantly increased the expression of α-SMA and CTGF, which were attenuated by additional treatment with losartan.
CONCLUSION
Losartan inhibited the expression of TGF-β1 and fibrogenic molecules in human TM cells. Thus, losartan has the potential to decrease TM fibrosis in patients with CMV-induced hypertensive anterior uveitis.
Identifiants
pubmed: 31216320
doi: 10.1371/journal.pone.0218471
pii: PONE-D-19-01695
pmc: PMC6584002
doi:
Substances chimiques
ACTA2 protein, human
0
Actins
0
CCN2 protein, human
0
TGFB1 protein, human
0
Transforming Growth Factor beta1
0
Connective Tissue Growth Factor
139568-91-5
Protein-Lysine 6-Oxidase
EC 1.4.3.13
Losartan
JMS50MPO89
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0218471Commentaires et corrections
Type : ErratumIn
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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