Starr Marlene E, Evers B Mark, Saito Hiroshi
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 77555-0828, USA.
J Gerontol A Biol Sci Med Sci. 2009 Jul;64(7):723-30. doi: 10.1093/gerona/glp046. Epub 2009 Apr 17.
Increased mortality and overexpression of interleukin-6 (IL-6) during inflammatory stress are well-documented age-associated phenomena; however, the site of IL-6 overexpression is not entirely known. Here, we report that white adipose tissue is a major source of IL-6 in aged animals during lipopolysaccharide (LPS)-induced systemic inflammation. Among the various tissues examined, white adipose tissue from the epididymal fat pad (located in the abdominal cavity) expressed the highest level of IL-6 messenger RNA in both young and aged mice with a 5.5-fold higher level in the aged. Immunohistochemistry revealed that, within the adipose tissue, LPS-induced IL-6 expression is localized to both the adipocytes and stromal cells. Compared with age-matched wild-type mice, aged IL-6((-/-)) mice exhibited reduced mortality to LPS suggesting a deleterious effect of IL-6 overexpression in the aged. These results demonstrate that increased vulnerability to systemic inflammation with age is due in part, to augmented IL-6 production by the adipose tissue.
在炎症应激期间死亡率增加以及白细胞介素-6（IL-6）的过表达是充分记录的与年龄相关的现象；然而，IL-6过表达的部位并不完全清楚。在此，我们报告白色脂肪组织是脂多糖（LPS）诱导的全身炎症期间老年动物中IL-6的主要来源。在检查的各种组织中，来自附睾脂肪垫（位于腹腔）的白色脂肪组织在年轻和老年小鼠中均表达最高水平的IL-6信使核糖核酸，老年小鼠中的水平高5.5倍。免疫组织化学显示，在脂肪组织内，LPS诱导的IL-6表达定位于脂肪细胞和基质细胞。与年龄匹配的野生型小鼠相比，老年IL-6基因敲除小鼠对LPS的死亡率降低，表明IL-6在老年小鼠中过表达具有有害作用。这些结果表明，随着年龄增长对全身炎症的易感性增加部分归因于脂肪组织中IL-6产生的增加。
