(-)-Epigallocatechin-3-gallate induces interferon-λ2 expression to anti-influenza A virus in human bronchial epithelial cells (BEAS-2B) through p38 MAPK signaling pathway

Abstract

Background: (-)-Epigallocatechin-3-gallate (EGCG), a major component of green tea, has been found to inhibit the influenza virus. However, the mechanism of EGCG anti-influenza virus effect needs to be further explored. Methods: BEAS-2B cells were treated with different concentrations of EGCG or were treated with EGCG for different times. CCK8 assay was used to detect the cell viability, and quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay were employed to measure the interferon (IFN)-λ2 mRNA and protein expression levels. The phospho-p38 mitogen-activated protein kinase (P-p38 MAPK), phospho-extracellular signal-regulated kinase (P-ERK), and phospho-c-Jun N-terminal kinase (P-JNK) expression were tested by western blot. Then, p38 MAPK, ERK, and JNK inhibitor were used to study the effect of p38 MAPK, ERK, and JNK signaling pathways on IFN-λ2 expression. The BEAS-2B cells were treated with EGCG, EGCG and IFN λ2 neutralizing antibody or control antibody for 12 h, and were infected with influenza A virus (IAV) (H1N1) for 1 h. After 12 h, nucleoprotein (NP) mRNA and protein expression levels of H1N1 were assessed by qRT-PCR and western blot. Results:The IFN-λ2 mRNA and protein expression levels in BEAS-2B cells were up-regulated after EGCG (treatment in time-and dose-dependent manners the concentration range from 0 to 50 μg/mL had no cytotoxicity). Meanwhile, the P-p38 MAPK, P-ERK, and P-JNK expression levels were up-regulated.IFN-λ2 mRNA and protein expression was inhibited after p38 MAPK inhibitor pre-treatment, but not by ERK and JNK inhibitors. Furthermore, the expression of H1N1 NP gene and protein decreased after EGCG pre-treatment, while IFN-λ2 neutralizing antibody attenuated the effect of EGCG inhibiting the expression of H1N1 NP gene and protein.Conclusions: EGCG inhibited IAV H1N1 by inducing the expression of IFN-λ2 in BEAS-2B cells through the p38 MAPK signaling pathway.

Antiinflammatory phytochemicals against virus‐induced hyperinflammatory responses: Scope, rationale, application, and limitations

“…For instance, 600–900 mg/day EGCG supplementation has been suggested to limit cytokine storm associated with SARS‐CoV‐2 infection, likely by inhibiting STAT‐1/3 and NFκB ‐dependent signaling (Menegazzi et al, 2020). Others have shown that EGCG in a dose and time‐dependent manner, elevated the mRNA and protein expression of the pro‐inflammatory interferon‐λ2 in human bronchial epithelial cells that were infected with influenza A virus (H1N1) (Zhu, Ou, Zhou, Yang, & Bie, 2020). Further, while EGCG pre‐treatment lowered the H1N1 nucleoprotein expression, IFN‐λ2 neutralizing antibody diminished the effects of EGCG.…”

Epigallocatechin Gallate: A Multifaceted Molecule for Neurological Disorders and Neurotropic Viral Infections

“…130 It inhibits IAV H1N1 by triggering the expression of IFN-λ2 in BEAS-2B cells via the p38 MAPK signaling pathway. 131 Epstein−Barr virus (EBV) is in continuous heed for its reach and infection to the CNS. 132,133 Numerous natural compounds can be a potential species to target its infectivity.…”

Integrated Analysis of microRNAs and Metabolomics in Rat’s Serum Reveals Multi-action Modes of Qingfei Paidu Decoction for COVID-19 Treatment

“…Involving regulation of immunity and in ammatory cytokines [125,126], virus infection, e.g., SARS-CoV-2, DHAV, PDCoV, RSV [125,[127][128][129][130][131] MAPK signaling pathway Involving regulation of immunity and in ammatory cytokines [132][133][134][135][136][137], virus infection, e.g., PDCoV, HIV, H1N1, SARS-CoV-2, FMDV, IAV [133][134][135][136][137][138][139][140][141][142][143][144] signaling pathways regulating pluripotency of stem cells…”