Green tea polyphenol EGCG suppresses cigarette smoke condensate-induced NF-κB activation in normal human bronchial epithelial cells

Abstract

Cigarette smoke is a powerful inducer of inflammatory responses resulting in disruption of major cellular pathways with transcriptional and genomic alterations driving the cells towards carcinogenesis. Cell culture and animal model studies indicate that (À)-epigallocatechin-3-gallate (EGCG), the major polyphenol present in green tea, possesses potent anti-inflammatory and antiproliferative activity capable of selectively inhibiting cell growth and inducing apoptosis in cancer cells without adversely affecting normal cells. Here, we demonstrate that EGCG pretreatment (20-80 lM) of normal human bronchial epithelial cells (NHBE) resulted in significant inhibition of cigarette smoke condensate (CSC)-induced cell proliferation. Nuclear factor-jB (NF-jB) controls the transcription of genes involved in immune and inflammatory responses. In most cells, NF-jB prevents apoptosis by mediating cell survival signals. Pretreatment of NHBE cells with EGCG suppressed CSC-induced phosphorylation of IjBa, and activation and nuclear translocation of NFjB/p65. NHBE cells transfected with a luciferase reporter plasmid containing an NF-jB-inducible promoter sequence showed an increased reporter activity after CSC exposure that was specifically inhibited by EGCG pretreatment. Immunoblot analysis showed that pretreatment of NHBE cells with EGCG resulted in a significant downregulation of NF-jB-regulated proteins cyclin D1, MMP-9, IL-8 and iNOS. EGCG pretreatment further inhibited CSC-induced phosphorylation of ERK1/2, JNK and p38 MAPKs and resulted in a decreased expression of PI3K, AKT and mTOR signaling molecules. Taken together, our data indicate that EGCG can suppress NF-jB activation as well as other pro-survival pathways such as PI3K/AKT/mTOR and MAPKs in NHBE cells, which may contribute to its ability to suppress inflammation, proliferation and angiogenesis induced by cigarette smoke.

Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

“…60,61 Therefore, increased RelA/p65 expression is possibly because of increased phosphorylation of RelA/p65 on ser276 as our results show. Consistent with in vitro studies, 62 CS exposure also induced the phosphorylation of RelA/p65 on ser536 in the lungs. Furthermore, the basal level of phosphorylation of RelA/p65 on ser536 was also increased in phoxϪ/Ϫ and gp91 phoxϪ/Ϫ mice compared to the airexposed control WT mice.…”

Antioxidant effects of green tea and its polyphenols on bladder cells

“…In neuronal cells, EGCG has been suggested to induce PKC activity, resulting in neuroprotection (Mandel and Youdin, 2004). Also, NF-κB inhibition has been shown to suppress oxidative stress-induced epithelial cell cytotoxicity/death (Jin et al, 2007;Syed et al, 2007). We speculate that similar signaling mechanisms mediate PP-60, ECG and EGCG bladder cytoprotection, and further studies are underway to probe changes in gene expression with catechin treatment.…”

Reduction of IKKα Expression Promotes Chronic Ultraviolet B Exposure-Induced Skin Inflammation and Carcinogenesis

“…[46][47][48] Those studies showed that chemoprevention agents including grape seed proanthocyanidins, epigallocatechin-3-gallate, and resveratrol repressed UVB-induced nuclear NF-B activity and cytosol IKK␣ levels in the mouse skin or keratinocytes, [46][47][48] suggesting that elevated IKK␣ levels may contribute to activation of NF-B after treatment with UVB. However, in the current study, we showed that NF-B activity was higher in Ikk␣ ϩ/Ϫ than in wild-type keratinocytes and that reduction in IKK␣ expression promoted UVB-induced skin carcinogenesis.…”