TNF and IL-6 mediate MIP-1α expression in bleomycin-induced lung injury
TNF and IL-6 mediate MIP-1α expression in bleomycin-induced lung injury
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DOI：
10.1002/jlb.64.4.528
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发表时间：
1998-10-01
影响因子：
5.5
通讯作者：
Kunkel, SL
中科院分区：
文献类型：
--
作者：
Smith, RE;Strieter, RM;Kunkel, SL
以前，巨噬细胞炎性蛋白-1 α C-C趋化因子家族的成员MIP-1 α（MIP-1 α）与博来霉素诱导的肺纤维化（人类疾病特发性肺纤维化的模型）有关。在博来霉素攻击的CBA/J小鼠中，用抗MIP-1 α抗体中和MIP-1 α蛋白显著减弱单核吞噬细胞募集和肺纤维化。然而，在博来霉素诱导的损伤中MIP-1 α表达的特异性刺激还没有被表征。在这份报告中，两个介质的炎症反应，博莱霉素，肿瘤坏死因子（TNF）和白细胞介素-6（IL-6），被评估为假定的刺激MIP-1 α表达后，博莱霉素在CBA/J小鼠的挑战。在博来霉素激发后的时间点，在博来霉素处理的CBA/J小鼠的支气管肺泡灌洗液（BAL）液和肺匀浆中检测到生物活性TNF和IL-6水平升高，这先于MIP-1 α蛋白表达。用可溶性TNF受体（sTNFr）或抗IL-6抗体治疗博来霉素攻击的小鼠显著降低肺中MIP-1 α蛋白表达。此外，正常肺泡巨噬细胞分泌的MIP-1 α蛋白水平升高的治疗与TNF加IL-6或博莱霉素加IL-6，但不是TNF，博莱霉素，或IL-6单独。最后，当单独用TNF处理时，与对照组相比，从博来霉素攻击小鼠的BAL液中回收的白细胞分泌更高水平的MIP-1 α蛋白。基于本文提供的时间数据，我们认为TNF和IL-6是细胞因子网络的一部分，该网络调节促纤维化炎性病变中MIP-1 α蛋白表达，并对博莱霉素内给药产生反应。
Previously, macrophage inflammatory protein-1 alpha (MIP-1 alpha), a member of the C-C chemokine family, has been implicated in bleomycin-induced pulmonary fibrosis, a model of the human disease idiopathic pulmonary fibrosis, Neutralization of MIP-1 alpha protein with anti-MIP-1 alpha antibodies significantly attenuated both mononuclear phagocyte recruitment and pulmonary fibrosis in bleomycin-challenged CBA/J mice, However, the specific stimuli for MIP-1 alpha expression in the bleomycin-induced lesion have not been characterized. In this report, two mediators of the inflammatory response to bleomycin, tumor necrosis factor (TNF) and interleukin-6 (IL-6), were evaluated as putative stimuli for MIP-1 alpha expression after bleomycin challenge in CBA/J mice. Elevated levels of bioactive TNF and IL-6 were detected in bronchoalveolar lavage (BAL) fluid and lung homogenates from bleomycin-treated CBA/J mice at time points post-bleomycin challenge, which precede MIP-1 alpha protein expression. Treatment of bleomycin-challenged mice with soluble TNF receptor (sTNFr) or anti-IL-6 antibodies significantly decreased MIP-1 alpha protein expression in the lungs. Furthermore, normal alveolar macrophages secreted elevated levels of MIP-1 alpha protein in response to treatment with TNF plus IL-6 or bleomycin plus IL-6, but not TNF, bleomycin, or IL-6 alone. Finally, leukocytes recovered from the BAL fluid of bleomycin-challenged mice secreted higher levels of MIP-1 alpha protein, compared to controls, when treated with TNF alone. Based on time data presented here, we propose that TNF and IL-6 are part of a cytokine network that modulates MIP-1 alpha protein expression in the profibrotic inflammatory lesion during the response to intratracheal bleomycin challenge.