کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2568851 1128491 2013 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin
چکیده انگلیسی

The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures.

Figure optionsDownload high-quality image (272 K)Download as PowerPoint slideHighlights
► Obesity modulates inflammatory markers in BAL fluid after LPS exposure.
► Obese animals have a unique transcriptional signature in lung after LPS exposure.
► Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung.
► Toxicant-specific biomarkers predict exposure independent of systemic inflammation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 267, Issue 2, 1 March 2013, Pages 137–148
نویسندگان
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