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Back to 2015 Annual Meeting Program Inhibition of Mast Cells Degranulation Protects Liver From LPS Induced Inflammation Through Hypothalamic - Pituitary - Thyroid Axis Xiqiao Zhou*1, Shu Zhang1, Hongquan Dong1, Ying Wang2, Junjun Yan1, Lin Lin1 1Gastroenterology, The first Affiliated Hospital of Nanjing Medical University, Nanjing, China; 2Gastroenterology, Jiangsu Province Geriatric Hospital, Nanjing, China The hypothalamus-pituitary-adrenal (HPA) axis is activated during an immune challenge to liberate energy and modulate immune responses via feedback and regulatory mechanisms. Inflammatory cytokines and prostaglandins are known contributors to HPA activation. Mast cell activation and degranulation can result in the release of powerful pro-inflammatory mediators such as histamine and cytokines. Cromolyn, which is the mast cell stabilizer, may be able to inhibit the release of some cytokines, as it has been shown to inhibit Tumor necrosis factor-alpha (TNF-α) production from rat mast cells. While a functional involvement of peripheral mast cells in inflammation is well established, the role of central nervous system (CNS) mast cells is not well understood. We study the effect of hypothalamic mast cells degranulation on LPS induced liver inflammation in rats. METHODS: Sprague-Dawley Rats (male, 200g) model of inflammation was generated with lipopolysaccharide (LPS). Hypothalamic stereotactic injection with cromolyn (200mg/kg) was given 30minuntes before LPS (1mg/Kg) intraperitoneal injection (n=6). Hypothalamic homogenates and serum were then collected. TNF-α, inflammatory cytokines interleukin-6 (IL-6) and hormone levels were measured using enzyme linked immunosorbent assay (ELISA). MAPK signals were detected by western-blot. HE staining was used to hepatic histopathology analysis. RESULTS: LPS induced liver inflammation, decreased the level of hypothalamic releasing hormone(CRH) in brain homogenates, increased serum thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and thyroxine (T3) , which could be partly abolished by cromolyn. There is no difference in serum cortisol level. Cromolyn also could decrease LPS-induced release of TNF-α and IL-6 . We also found that cromolyn could partly abolish LPS-induced phosphorylation of JNK and ERK in liver homogenates. CONCLUSION: Our results indicate that inhibition of hypothalamic mast cells degranulation can protect liver from LPS induced inflammation through hypothalamic - pituitary - thyroid axis. Our study provides valuable information for the control of inflammatory diseases. Back to 2015 Annual Meeting Program |
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