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

Autor: Jiaming Qian, Anping Ni, Hong Yang, Shujun Wang, Yaling Dou, Rui Zhang
Rok vydání: 2017
Předmět:
Zdroj: FEBS Open Bio
ISSN: 2211-5463
DOI: 10.1002/2211-5463.12334
Popis: Cytomegalovirus (CMV) infection is associated with glucocorticoid resistance in ulcerative colitis (UC) and may exacerbate the disease course. However, the underlying pathogenicity remains unclear. The aim of this study was to explore possible underlying mechanisms during CMV latency and lytic infection in the human mononuclear cell line THP-1. Latent and activated CMV infection cell models were established. We performed real-time PCR and western blotting to examine changes in glucocorticoid receptors (GRs) during CMV latency and activation. Pro-inflammatory and anti-inflammatory cytokines were detected by ELISA. After UV-inactivated CMV infection, GRs and cytokines were also examined. The expression of GRs was elevated in the reactivation group. An increased ratio of GR β/α and phosphorylation of GRα in the CMV reactivation group may explain refractory response to steroids. During CMV lytic infection, pro-inflammatory cytokines IL-6 and TNF-α increased remarkably and anti-inflammatory cytokine IL-5 decreased, which may exacerbate UC. GR and cytokines were unchanged in the UV-inactivated CMV infection group. Changes in the number and function of GRs may account for glucocorticoid resistance in CMV reactivation. The imbalance of pro- and anti-inflammatory cytokines may be related to severe inflammation.
Databáze: OpenAIRE