Immune response of macrophages from young and aged mice to the oral pathogenic bacterium Porphyromonas gingivalis.
Immune response of macrophages from young and aged mice to the oral pathogenic bacterium Porphyromonas gingivalis.
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DOI：
10.1186/1742-4933-7-15
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发表时间：
2010-11-29
期刊：
影响因子：
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通讯作者：
Gibson FC 3rd
中科院分区：
文献类型：
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作者：
Shaik-Dasthagirisaheb YB;Kantarci A;Gibson FC 3rd
牙周病是一种慢性炎症性牙龈疾病，在严重的情况下会导致牙齿脱落。牙龈卟啉单胞菌（Porphyromonas gingivalis，Pg）是一种与全身性牙周病密切相关的细菌。牙周病的临床发病年龄一般在40岁以上。关于衰老对与牙周病相关的炎症的影响，人们知之甚少。在本研究中，我们研究了年轻（2个月）和老年（1岁和2岁）小鼠骨髓源性巨噬细胞（BMM）对Pg菌株381的免疫反应。PG诱导细胞因子的大量表达;肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6和IL-10，趋化因子;中性粒细胞趋化蛋白（KC）、巨噬细胞集落刺激因子（MCP）-1、巨噬细胞炎性蛋白（MIP）-1α和活化后正常T细胞表达和分泌的调节因子（RANTES），以及一氧化氮（NO，以亚硝酸盐测量）和来自年轻小鼠的BMM的前列腺素E2（PGE 2）。与2月龄和1岁龄的BMM相比，2岁龄的BMM对Pg的反应产生的TNF-α、IL-6和NO显著减少。我们没有观察到BMM对PG产生的IL-1β、IL-10和PGE 2水平有任何差异。2月龄和1岁龄的BMM产生的所有趋化因子水平相似，但MCP-1除外，MCP-1在1岁龄的BMM中降低。与2个月和1岁年龄组相比，2岁年龄组的BMM产生的MCP-1和MIP-1α显著减少。不同年龄组之间RANTES的产生无差异。采用Pg减毒突变体，缺乏主要菌毛（Pg DPG 3），我们观察到降低的能力的突变体刺激炎症介质表达从BERNIA相比，Pg 381，无论年龄。综上所述，这些结果支持衰老作为老年宿主BMM对牙周病原体Pg观察到的免疫应答降低的重要方面。
Periodontal disease is a chronic inflammatory gum disease that in severe cases leads to tooth loss. Porphyromonas gingivalis (Pg) is a bacterium closely associated with generalized forms of periodontal disease. Clinical onset of generalized periodontal disease commonly presents in individuals over the age of 40. Little is known regarding the effect of aging on inflammation associated with periodontal disease. In the present study we examined the immune response of bone marrow derived macrophages (BMM) from young (2-months) and aged (1-year and 2-years) mice to Pg strain 381. Pg induced robust expression of cytokines; tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10, chemokines; neutrophil chemoattractant protein (KC), macrophage colony stimulating factor (MCP)-1, macrophage inflammatory protein (MIP)-1α and regulated upon activation normal T cell expressed and secreted (RANTES), as well as nitric oxide (NO, measured as nitrite), and prostaglandin E2 (PGE2) from BMM of young mice. BMM from the 2-year age group produced significantly less TNF-α, IL-6 and NO in response to Pg as compared with BMM from 2-months and 1-year of age. We did not observe any difference in the levels of IL-1β, IL-10 and PGE2 produced by BMM in response to Pg. BMM from 2-months and 1-year of age produced similar levels of all chemokines measured with the exception of MCP-1, which was reduced in BMM from 1-year of age. BMM from the 2-year group produced significantly less MCP-1 and MIP-1α compared with 2-months and 1-year age groups. No difference in RANTES production was observed between age groups. Employing a Pg attenuated mutant, deficient in major fimbriae (Pg DPG3), we observed reduced ability of the mutant to stimulate inflammatory mediator expression from BMMs as compared to Pg 381, irrespective of age. Taken together these results support senescence as an important facet of the reduced immunological response observed by BMM of aged host to the periodontal pathogen Pg.