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A1417 - Anti-Inflammatory Effects of Sulforaphane on Adipose Tissue Macrophages Isolated from Obese Subjects with and Without Asthma
Author Block: E. J. Williams1, L. Guilleminault2, B. S. Berthon2, K. J. Baines2, P. G. Gibson3, T. Wright4, C. Karihaloo4, M. Gately5, L. G. Wood2; 1Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia, 2Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, NSW, Australia, 3Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, Australia, 4Department of Surgery, John Hunter Hospital, Newcastle, Australia, 5Department of Surgery, Lake Macquarie Private Hospital, New Lambton, Australia.
Rationale: Systemic inflammation contributes to the development of obesity related co-morbidities including cardiovascular disease, type 2 diabetes and cancer. It has also previously been shown to be a predictor of future exacerbations in asthma. Systemic inflammation is a key feature of obesity. In obesity, adipose tissue macrophages (ATMs) drive systemic inflammation by releasing pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. Sulforaphane is a dietary antioxidant with anti-inflammatory properties and is naturally found in cruciferous vegetables such as broccoli, brussel sprouts, cabbage and cauliflower. Sulforaphane is known as an indirect antioxidant as it works by activating the transcription factor, nuclear factor erythroid 2-related factor 2 (NRF2), thereby inducing the transcription and translation of antioxidant enzymes such as heme-oxygenase-1 (HMOX1), superoxide dismutase-1 (SOD1) and glutathione peroxidase (GPx). This study examined the effects of sulforaphane on ATMs, in order to assess its potential for reducing the systemic pro-inflammatory effects of adipose tissue. Methods: Primary ATMs were isolated from visceral fat obtained from obese (BMI ≥ 30kg/m2) subjects with (n=3) and without (n=7) asthma, undergoing laparoscopic sleeve gastrectomy. ATMs were then pre-treated with control (DMSO) or sulforaphane (40µM) for 3 hours before being stimulated with lipopolysaccharide (LPS; 1ng/ml) for 15 hours. Treatment with media for 15 hours without LPS was also performed to assess cytokine production of unstimulated monocytes. Cell culture supernatants were then collected and assayed for TNF-α and IL-1β, using enzyme-linked immunosorbent assay (ELISA). Results: Pre-treatment with sulforaphane significantly reduced ATM production of TNF-α in both the asthmatic group (243 (113, 265) pg/mL (control) versus 8 (2, 15) pg/mL (sulforaphane); p=0.043) and the non-asthmatic group (201.9 (76, 482) pg/mL versus 5 (1, 36) pg/mL; p=0.006). IL-1β was also significantly reduced in the asthmatic group (83 (68, 95) pg/mL versus 1 (0, 1) pg/mL; p=0.043) and non-asthmatic group (55 (15, 267) pg/ml versus 2 (1, 3) pg/ml; p=0.001) following sulforaphane treatment.
Conclusions: Sulforaphane pre-treatment reduced LPS-induced inflammatory cytokine production in ATMs from obese asthmatic and non-asthmatic subjects. Therefore increasing the consumption of cruciferous vegetables which contain sulforaphane, or supplementing sulforaphane, may help to reduce obesity induced systemic inflammation. This has the potential to reduce risk of chronic disease, as well as reducing risk of exacerbations in obese asthmatics. Funding: John Hunter Hospital Charitable Trust