Alteration of glucocorticoid receptors and exacerbation of inflammation during lytic cytomegalovirus infection in <scp>THP</scp>‐1 cells

Wang, Shujun; Dou, Yaling; Yang, Hong; Ni, Anping; Zhang, Rui; Qian, Jiaming

doi:10.1002/2211-5463.12334

Cited by 10 publications

(7 citation statements)

References 23 publications

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“…In addition, corticosteroids facilitate IE genes’ transcription [ 110 ] and reactivation of latent virus in infected cells [ 111 ]. In turn, it has also been proposed that CMV alters the expression of glucocorticoid receptors (GR), with an increased ratio of GR β/α and phosphorylation of the α isoform, leading to refractory response to these immunomodulator drugs during lytic infection [ 112 ].…”

Section: Inflammation and Immunosuppressive Therapies Contribute Tmentioning

confidence: 99%

Cytomegalovirus and Inflammatory Bowel Diseases (IBD) with a Special Focus on the Link with Ulcerative Colitis (UC)

et al. 2020

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Cytomegalovirus (CMV) infects approximately 40% of adults in France and persists lifelong as a latent agent in different organs, including gut. A close relationship is observed between inflammation that favors viral expression and viral replication that exacerbates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBDs), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation and T helper cell (TH) 2 cytokines, together with immunomodulatory drugs used for controlling flare-ups, favor viral reactivation within the gut, which, in turn, increases mucosal inflammation, impairs corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in the case of CMV colitis), and enhances the risk for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during inflammatory bowel diseases (IBD) and underlines the interest of using ganciclovir for treating flare-ups associated to CMV colitis in UC patients.

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Section: Inflammation and Immunosuppressive Therapies Contribute Tmentioning

confidence: 99%

Cytomegalovirus and Inflammatory Bowel Diseases (IBD) with a Special Focus on the Link with Ulcerative Colitis (UC)

et al. 2020

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“…Recently, these observations were confirmed in an independent cohort, where CMV infection was associated with an almost identical immunophenotype approximately 15 years postinstitutionalization and adoption (Reid et al 2019). Furthermore, lifelong, latent CMV infection occurs in a small percentage of hematopoietic progenitor cells (Slobedman, et al, 2004), and it has significant effects on GR transcription and translation (Wang et al, 2017).…”

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confidence: 99%

Glucocorticoid receptor signaling in leukocytes after early life adversity

et al. 2019

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Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had been exposed to ELA (separation from parents and/or institutionalization followed by adoption; n = 40) or had been reared by their biological parents (n = 72). Expression of the strict GR target genes FKBP5 and GILZ as well as total and 1F and 1H GR transcripts were similar between groups. Furthermore, there were no differences in GR sensitivity, examined by the effects of dexamethasone on IL6 production in LPS-stimulated whole blood. Although we did not find differences in methylation at the GR 1F exon or promoter region, we identified a region of the GR 1H promoter (CpG 1-9) that showed lower methylation levels in ELA. Our results suggest that peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered GR response to the perturbed HPA axis and glucocorticoid (GC) profile, although we are limited in our measures of GR activity and time points.

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“…Glucocorticoid resistance was recently reported in cases of CMV ulcerative colitis because of receptor alterations [18]. Cases 3 and 4 had recurrences of the anterior chamber inflammation while being treated with topical steroids and GCV.…”

Section: Discussionmentioning

confidence: 91%

Relationships between the clinical characteristics and copy numbers of DNA of cytomegalovirus determined by real-time PCR

Yoshimura

Araki-Sasaki

Toyokawa³

et al. 2020

Int Ophthalmol

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Purpose To determine whether there is a correlation between the clinicals characteristics including various types of keratic precipitates and the copy numbers of the DNA of cytomegalovirus (CMV) in eyes with CMV corneal endotheliitis. Methods We reviewed the medical charts of four cases of corneal endotheliitis that were CMV-positive. We have classified types of clinical phenomenon into four types: coin-shaped KPs, sectoral corneal edema with or without Khodadoust line-like KPs, mutton-fat KPs, and fine KPs and have graded their severity. We also determined the copy numbers of the DNA of CMV in the aqueous humor by real-time polymerase chain reaction before and during the treatment. We evaluated the correlation between the patterns of clinical characteristics and copy number of the DNA of CMV. Results There were clinical improvements in all eyes following topical ganciclovir in conjunction with low dose of topical steroid treatment, with or without oral valganciclovir. The clinical characteristics and the copy numbers of the DNA of CMV varied during the treatment period. The presence of coin-shaped KPs was correlated with high copy numbers (105–103 copies/ml) of the DNA of CMV. The copy numbers of the DNA of CMV with sectoral corneal edema with or without Khodadoust line-like KPs ranged from 104 to 102 copies/ml, and it was occasionally accompanied by high intraocular pressure. Mutton-fat KPs were observed inferiorly, sometimes together with coin-shaped KPs and sectoral corneal edema, or solely. The copy numbers in eyes with mutton-fat KPs varied and occasionally less than the cutoff level. Fine-pigmented KPs were observed after the resolution of the endotheliitis, and no DNA of CMV was detected in the aqueous humor. Conclusions Careful observations of the clinical characteristics such as the KPs and corneal edema might be helpful in estimating the amount of the DNA of CMV in eyes with corneal endotheliitis.

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Alteration of glucocorticoid receptors and exacerbation of inflammation during lytic cytomegalovirus infection in THP‐1 cells

Cited by 10 publications

References 23 publications

Cytomegalovirus and Inflammatory Bowel Diseases (IBD) with a Special Focus on the Link with Ulcerative Colitis (UC)

Cytomegalovirus and Inflammatory Bowel Diseases (IBD) with a Special Focus on the Link with Ulcerative Colitis (UC)

Glucocorticoid receptor signaling in leukocytes after early life adversity

Relationships between the clinical characteristics and copy numbers of DNA of cytomegalovirus determined by real-time PCR

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