Exposure to Toluene Diisocyanate (TDI) Induces IL-8 Production from Bronchial Epithelial Cells: Effect of Pro-inflammatory Cytokines

Abstract

This investigation was designed to confirm IL-8 production from human bronchial epithelial cells with toluene diisocyanate (TDI) exposure and to examine the effects of pro-inflammatory cytokine and dexamethasone. We cultured Beas-2B, a bronchial epithelial cell line with TDI-HSA conjugate and compared with those without conjugate. IL-8 in the supernatant was measured by ELISA. To evaluate the effect of proinflammatory cytokines, peripheral blood mononuclear cells (PBMC) were collected from TDI- and non-TDI asthma patients, and were added to the epithelial cell culture. Dexamethasone or antibodies to TNF-alpha and IL-1beta were pre-incubated with PBMC supernatant. There was a significant production of IL-8 from bronchial epithelial cells with addition of TDI-HSA conjugate in a dose-dependent manner, which was significantly augmented with addition of PBMC supernatant. Higher production of IL-8 was noted with addition of PBMC supernatant from TDI-asthma patients than in those from non-TDI asthma patients. IL-1beta and IL-1beta/TNF alpha antibodies were able to suppress the IL-8 productions. Pre-treatment of dexamethasone induced dose-dependent inhibition of the IL-8 production. These results suggest that the IL-8 production from bronchial epithelial cells contribute to neutrophil recruitment occurring in TDI-induced airway inflammation. IL-1beta released from PBMC of TDI-induced asthma patients may be one of the pro-inflammatory cytokines to enhance IL-8 production.

Tissue Transglutaminase Can Be Involved in Airway Inflammation of Toluene Diisocyanate-Induced Occupational Asthma

“…The relationship between specific IgE to this conjugate and IgG to tTG level was observed. Many stimuli, including isocyanate and proinflammatory cytokines, induce cytokine and chemokine production and cellular recruitment in bronchial epithelial cells [3,20,21]. TDI-generated ROS may induce barrier dysfunction in epithelial cells and reduce antioxidant levels [22][23][24][25].…”

TOLUENE DIISOCYANATE (TDI) INDUCES PRODUCTION OF INFLAMMATORY CYTOKINES AND CHEMOKINES BY BRONCHIAL EPITHELIAL CELLS VIA THE EPIDERMAL GROWTH FACTOR RECEPTOR AND p38 MITOGEN-ACTIVATED PROTEIN KINASE PATHWAYS

“…The mechanism by which cytokine production was enhanced by TDI-HSA conjugate involved the p38 MAP kinase and EGFR pathways. In previous reports, Lee and colleagues showed that TDI-HSA augmented IL-8 production by a bronchial epithelial line after stimulation by TDI-HSA alone, and with lymphocytes obtained from TDI-induced asthma patients [8]. In primary bronchial epithelial cells, vapor TDI was shown to stimulate IL-6 and IL-1b production [21].…”

“…CS augmented interleukin (IL)-8 production [6] and DEP were shown to induce granulocyte-macrophage-colony-stimulating factor (GM-CSF) secretion [7] by bronchial epithelial cells. It has already been showed that TDI-human serum albumin (HSA) conjugate induces IL-8 production in BEAS-2B cells [8]. But little is known that other cytokine and chemokine production.…”

Signalling pathway of isophorone diisocyanate-responsive interleukin-8 in airway smooth muscle cells

“…IL-8 has been reported to trigger calcium release, contraction and migration in BSMCs through functional CXC chemokine receptor (CXCR)1 and CXCR2 [18,19]. Another isocyanate, toluene diisocyanate, has been found to increase bronchial epithelial cells production of IL-8, which in turn recruits neutrophils, resulting in an inflammatory response [20,21]. However, the role of IL-8 on IPDI-related asthma remains unknown.…”