Differential effects of cigarette smoke extract on cytokine production from IL‐1beta‐activated mast cells

Abstract

Human mast cells are multifunctional cells capable of a wide variety of inflammatory responses and associated with allergy, asthma, and atherosclerosis. Our previous studies have shown that IL‐1β activates human mast cells to produce selected inflammatory cytokines. We examined effects of cigarette smoke extract (CSE) on the production of inflammatory cytokines from IL‐1β‐activated human mast cells. Mainstream (Ms) and Sidestream (Ss) cigarette smoke were collected onto fiber filters and extracted in RPMI‐1640 medium. Two ml of HMC‐1 at 1 × 106 cells/mL were cultured with Ms and Ss CSE at various concentrations in the presence or absence of IL‐1β (10 ng/mL) for 24 hrs. The supernatants were harvested and assayed for IL‐6, IL‐8, and MCP‐1 by ELISA. The Ms and Ss CSE (32.5 to 500 μg/mL) alone induced either no or trace amounts of cytokines from HMC‐1. However, both Ms and Ss CSE significantly increased IL‐6 and IL‐8 production (all p < 0.001) from IL‐1β‐activated HMC‐1 in a dose dependent fashion, except Ms CSE at 500 μg/mL, which significantly decreased IL‐6 production (p < 0.0001). Contrarily, both Ms and Ss CSE at concentrations from 62.5 to 500 μg/mL, but not 32.5 μg/mL, significantly inhibited MCP‐1 production (all p < 0.05) by IL‐1β‐activated HMC‐1 in a dose dependent fashion. The effects of Ms CSE appeared to be more potent than that of Ss CSE. The results show that CSE had differential effects on the production of inflammatory cytokines from IL‐1β‐activated mast cells, which may partially explain why cigarette smoke contributes to lung and cardiovascular diseases. (Supported by the Ruth R. Harris Endowment and RDC of ETSU)