Enhanced effects of cigarette smoke extract on inflammatory cytokine expression in IL-1beta-activated human mast cells were inhibited by Baicalein via regulation of the NF-kappaB pathway

Human mast cells are capable of a wide variety of inflammatory responses and play a vital role in the pathogenesis of inflammatory diseases such as allergy, asthma, and atherosclerosis. We have reported that cigarette smoke extract (CSE) significantly increased IL-6 and IL-8 production in IL-1-activated human mast cell line (HMC-1).

Baicalein (BAI) has anti-inflammatory properties and inhibits IL-1- and TNF--induced inflammatory cytokine production from HMC-1. The goal of the present study was to examine the effect of BAI on IL-6 and IL-8 production from CSE-treated and IL-1-activated HMC-1.

Methods: Main-stream (Ms) and Side-stream (Ss) cigarette smoke were collected onto fiber filters and extracted in RPMI-1640 medium. Two ml of HMC-1 at 1 x 106 cells / mL were cultured with CSE in the presence or absence of IL-1 (10 ng / mL) for 24 hrs.

A group of HMC-1 cells stimulated with both IL-1beta (10 ng/ml) and CSE was also treated with BAI. The expression of IL-6 and IL-8 was assessed by ELISA and RT-PCR.

NF-kappaB activation was measured by electrophoretic mobility shift assay (EMSA) and IkappaBalpha degradation by Western blot.

Results: Both Ms and Ss CSE significantly increased IL-6 and IL-8 production (p <0.001) in IL-1-activated HMC-1.

CSE increased NF-kappaB activation and decreased cytoplasmic IkappaBalpha proteins in IL-1beta-activated HMC-1. BAI (1.8 to 30 muM) significantly inhibited production of IL-6 and IL-8 in a dose-dependent manner in IL-1beta-activated HMC-1 with the optimal inhibition concentration at 30 muM, which also significantly inhibited the enhancing effect of CSE on IL-6 and IL-8 production in IL-1beta-activated HMC-1.

BAI inhibited NF-kappaB activation and increased cytoplasmic IkappaBalpha proteins in CSE-treated and IL-1beta-activated HMC-1.

Conclusions: Our results showed that CSE significantly increased inflammatory cytokines IL-6 and IL-8 production in IL-1-activated HMC-1.

It may partially explain why cigarette smoke contributes to lung and cardiovascular diseases. BAI inhibited the production of inflammatory cytokines through inhibition of NF-kappaB activation and IkappaBalpha phosphorylation and degradation.

This inhibitory effect of BAI on the expression of inflammatory cytokines induced by CSE suggests its usefulness in the development of novel anti-inflammatory therapies.

Author: David S ChiTa-Chang LinKenton HallTuanzhu HaChuanfu LiZong Doa WuThomas SoikeGuha Krishnaswamy
Credits/Source: Clinical and Molecular Allergy 2012, 10:3

Published on: 2012-02-06

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