RAGE mediates airway inflammation via the HDAC1 pathway in a toluene diisocyanate-induced murine asthma model

BackgroundExposure to toluene diisocyanate (TDI) is a significant pathogenic factor for asthma. We previously reported that receptor for advanced glycation end products (RAGE) plays a key role in TDI-induced asthma; however, the mechanism is not clear. Epigenetic alterations of histone deacetylase (HDAC) are associated with allergic asthma. However, its effect in TDI-induced asthma is not known. The purpose of this study was to determine the role of RAGE and HDAC1 in the regulation of airway inflammation using a TDI-induced asthma model.MethodsBALB/c mice were sensitized, and challenged by TDI to establish murine asthma models. FPS-ZM1 (RAGE inhibitor), JNJ-26482585 and romidepsin (HDAC inhibitor) were given intraperitoneally before each challenge. The human bronchial epithelial cell line 16HBE was stimulated by TDI-human serum albumin (TDI-HSA) in vitro. RAGE knockdown cells were constructed and evaluated, and MK2006 (AKT inhibitor) was used in in vitro experiments.ResultsIn the TDI-induced asthmatic mice, airway reactivity, the level of Th2 cytokines in lymph supernatant, IgE, airway inflammation, and goblet cell metaplasia were all significantly increased. The increases were suppressed by FPS-ZM1, JNJ-26482585, and romidepsin. The expression of HDAC1, RAGE, and p-AKT/t-AKT was also upregulated in TDI-induced asthmatic mice, and the expressions were attenuated by FPS-ZM1. Knockdown of RAGE attenuated the upregulation of HDAC1 and phospho-AKT (p-AKT) in 16HBE cells stimulated by TDI-HSA. Treatment with the AKT inhibitor MK2006 suppressed TDI-induced HDAC1 expression. ConclusionRAGE mediates airway inflammation in a TDI-induced murine asthma model, partly via the HDAC1 pathway. Key words: Toluene diisocyanate, asthma, histone deacetylase 1, advanced glycosylation end product receptor

Adsorption of Toluene Using Low Cost Adsorbent

Kertas kerja ini membincangkan tentang kecekapan penjerap yang lebih murah, iaitu tayar getah terbuang (DRT), dalam menyingkirkan toluena daripada fasa akuas. Penjerapan toluena pada tayar getah terbuang dikaji menggunakan sistem berkelompok pada suhu 25°C dan 30°C. Daripada kajian ini, didapati toluena dapat disingkirkan sehingga 70% dengan menggunakan julat kepekatan awalan antara 50 mg/l hingga 300 mg/l. Dengan menggunakan model keseimbangan terlelurus, iaitu model Langmuir dan Freundlich, keupayaan penjerapan maksimum dapat ditentukan. Daripada data eksperimen, terbukti bahawa walaupun kedua–dua model isoterma Langmuir dan Freundlich boleh menjelaskan data isoterma, tetapi penjerapan toluena pada DRT dapat ditunjukkan dengan lebih baik oleh isoterma Freudlich. Bagi nilai K Freundlich, keupayaan penjerapan ialah 6.6374 mg/l dan 7.7535 mg/l, pada suhu 25°C dan 30°C. Nilai eksponen n Freudlich adalah lebih daripada satu untuk kedua–dua suhu. Kata kunci: Toluena, penjerapan, isoterma, tayar getah terbuang, model isoterma Langmuir, model isoterma Freundlich This paper discusses the effectiveness of a less expensive adsorbent, a discarded rubber tyre (DRT) in removing toluene from aqueuos phase. Adsorption of toluene on a DRT has been studied by using batch system at 25 and 30°C. It was found that up to 70% of toluene was removed for the range of toluene initial concentrations studied between 50–300 mg/l. Using linearized forms of equilibrium models, namely Langmuir and Freundlich models, the maximum adsorptive capacities were determined. It was evident from the experimental data that, although both Langmuir and Freundlich isotherm models could describe the isotherm data, the adsorption of toluene on a DRT was described well by the Freundlich isotherm. For Freundlich K values, sorption capacities were 6.6374 and 7.7535 mg/l at 25 and 30°C, respectively. The values of Freundlich exponent n were greater than one for both temperatures. Key words: Toluene, adsoprtion, isotherms, discarded rubber tyre, Langmuir isotherm model, Freundlich isotherm model