Differential effects of ageing on cytokine and chemokine responses during type-1 (Mycobacterial) and type-2 (Schistosomal) pulmonary granulomatous inflammation in mice

Differential effects of ageing on cytokine and chemokine responses during type-1 (Mycobacterial) and type-2 (Schistosomal) pulmonary granulomatous inflammation in mice
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DOI:
10.1016/s0047-6374(01)00372-4
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发表时间:
2002-02-01
影响因子:
5.3
通讯作者:
Chensue, SW
Chensue, SW
中科院分区:
医学3区
文献类型:
--
作者:
Chiu, BC;Shang, XZ;Chensue, SW

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在小鼠6、12、18和24月龄时,评估了遗忘型1和2型肺肉芽肿形成过程中细胞因子和趋化因子的反应。病变是通过连接牛分枝杆菌纯化蛋白衍生物或可溶性曼氏血吸虫卵抗原的Sepharose珠栓塞诱导的。1型炎症在18个月时减轻,而2型肉芽肿直到24个月时才减轻。在1型引流淋巴结培养中,干扰素- γ (IFNgamma)在18个月时降至最低点,然后在24个月时部分恢复。相比之下,IL-4在2型培养中直到24个月才明显受损。1型和2型淋巴结培养在24个月时也显示出IL-13的减少,但矛盾的是IL-5的产生增加。肉芽肿肺中的趋化因子转录物显示出与年龄相关的改变。在type-1响应中。CXCL9(由IFNgamma诱导的单因子)随着年龄的增长而下降,然后在24个月时部分恢复,与淋巴结IFNgamma水平平行。MIP-2/CXCL2转录本。IP-10/CXCL10、MCP-1/CCL2和MCP-5/CCL12在24个月时升高。在2型反应中,MCP-1/CCL2、MCP-3/CCL7、MCP-5/CCL12和TARC/CCL17在24个月时与局部IL-4转录水平平行,但一些趋化因子转录物如KC/CXCL1和eotaxin/CCL11未受影响。这些发现表明,随着年龄的变化,Th1/Th2交叉调节压力和趋化因子的局部表达,细胞因子和趋化因子的反应会不同程度地降低。爱尔兰爱思唯尔科学有限公司出版。
Cytokine and chemokine responses during anamnestic type-1 and type-2 lung granuloma formation were evaluated in mice at 6, 12, 18 and 24-months of age. Lesions were induced by embolizing Sepharose beads coupled to Mycobacterium bovis purified protein derivative or soluble Schistmoma mansoni egg antigens. Type-1 inflammation was reduced by 18 months, whereas type-2 granulomas not Until 24 months of age. In type-1 draining lymph nodes cultures, interferon-gamma (IFNgamma) declined to a nadir by 18, and then partly recovered at 24 months. In contrast, IL-4 was not significantly impaired in type-2 Cultures until 24 months. Type-1 and 2 node cultures also displayed decreased IL-13, but paradoxically enhanced IL-5 production at 24 months. Chemokine transcripts in granulomatous lungs displayed age-related alterations. In the type-1 response. CXCL9 (monokine-induced by IFNgamma) declined with age then partly recovered at 24 months parallelling lymph node IFNgamma levels. Transcripts for MIP-2/CXCL2. IP-10/CXCL10, MCP-1/CCL2, and MCP-5/CCL12 increased at 24 months. In the type-2 response MCP-1/CCL2, MCP-3/CCL7, MCP-5/CCL12 and TARC/CCL17 collapsed at 24 months paralleling local IL-4 transcript levels, yet some chemokine transcripts such as KC/CXCL1 and eotaxin/CCL11 were unaffected. These findings suggest that cytokine and chemokine responses degrade differentially with age shifting Th1/Th2 crossregulatory pressures and local expression of chemokines. Published by Elsevier Science Ireland Ltd.