Brass David M, Hollingsworth John W, Fessler Michael B, Savov Jordan D, Maxwell Abby B, Whitehead Gregory S, Burch Lauranell H, Schwartz David A
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
J Allergy Clin Immunol. 2007 Jul;120(1):121-7. doi: 10.1016/j.jaci.2007.03.051. Epub 2007 May 18.
The contribution of IL-1beta signaling through the IL-1 type 1 receptor (IL-1R1) to the development of persistent LPS-induced airway disease has not been investigated.
To determine the importance of signaling through the IL-1 type 1 receptor in the development of LPS-induced airway disease.
We exposed IL-1R1-deficient (C57BL/6(IL-1RI-/-)) mice to an aerosol of LPS or filtered air for 1 day, 1 week, or 4 weeks.
After 4 weeks of LPS inhalation, C57BL/6(IL-1RI-/-) mice failed to develop significant submucosal thickening, whereas C57BL/6 mice had significantly thickened submucosa in small, medium, and large airways compared with those of unexposed control mice. Cell proliferation in the airways of both the 1-week and 4-week LPS-exposed C57BL/6(IL-1RI-/-) mice was significantly reduced compared with LPS-exposed C57BL/6 mice. mRNA for type III alpha-3 procollagen was significantly elevated over baseline in C57BL/6 yet remained unchanged compared with baseline in C57BL/6(IL-1RI-/-) mice after 1 week or 4 weeks of LPS inhalation. mRNA for tissue inhibitor of metalloprotease 1 in C57BL/6 mice in the 1-week and 4-week groups was significantly elevated over both control mice and C57BL/6(IL-1RI-/-) mice.
These data support the hypothesis that signaling through the IL-1 receptor modulates extracellular matrix homeostasis in response to inhaled LPS.
Attenuating IL-1R1-mediated signaling might be an effective therapy against the development of airway remodeling in chronic inflammatory diseases.
白细胞介素1β（IL-1β）通过白细胞介素1型受体（IL-1R1）发出的信号对持续性脂多糖（LPS）诱导的气道疾病发展的作用尚未得到研究。
确定通过IL-1型受体发出的信号在LPS诱导的气道疾病发展中的重要性。
我们将IL-1R1缺陷型（C57BL/6(IL-1RI-/-)）小鼠暴露于LPS气雾剂或过滤空气中1天、1周或4周。
吸入LPS 4周后，C57BL/6(IL-1RI-/-)小鼠未出现明显的黏膜下增厚，而与未暴露的对照小鼠相比，C57BL/6小鼠在小、中、大气道中均有明显增厚的黏膜下层。与暴露于LPS的C57BL/6小鼠相比，暴露于LPS 1周和4周的C57BL/6(IL-1RI-/-)小鼠气道中的细胞增殖明显减少。吸入LPS 1周或4周后，C57BL/6小鼠中III型α-3前胶原的mRNA水平显著高于基线，但与C57BL/6(IL-1RI-/-)小鼠的基线相比保持不变。1周和4周组的C57BL/6小鼠中金属蛋白酶组织抑制剂1的mRNA水平显著高于对照小鼠和C57BL/6(IL-/-)小鼠。
这些数据支持以下假设，即通过IL-1受体发出的信号可调节对吸入LPS的细胞外基质稳态。
减弱IL-1R1介导的信号传导可能是治疗慢性炎症性疾病中气道重塑发展的有效疗法。
