Bleomycin induces IL-8 and ICAM-1 expression in microvascular pulmonary endothelial cells

Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie
Falk FichtnerMichael Kasper

Abstract

To investigate the pathomechanisms of bleomycin-induced early inflammation of lung parenchyma which is known to result in pulmonary fibrosis, we examined the in vitro effect of bleomycin (BLM) on primary human pulmonary microvascular endothelial cells (HMVEC-L). After incubation of microvascular endothelial cells with BLM we detected an induced phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) by immunoblotting. Further, after BLM-exposure an increased concentration of interleukin-8 (IL-8) in culture supernatant and an increased expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on the cell surface have been observed. Real-time PCR revealed up-regulated mRNA expression levels of both, IL-8 and ICAM-1 after treatment with BLM. Finally, pre-treatment with a selective p38 MAPK-inhibitor, SB 203580, potently reduced the BLM-induced up-regulation of IL-8 expression but did not show any effect on expression of ICAM-1. These results demonstrate that BLM induces the expression of pro-inflammatory molecules in the pulmonary microvascular endothelium, which thereby may actively contribute to the development of early inflammation and later fibrosis of the lung. Furthermore, investigating the effect of an inhib...Continue Reading

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Citations

Sep 24, 2008·Antioxidants & Redox Signaling·Arshad Rahman, Fabeha Fazal
Oct 22, 2011·American Journal of Respiratory and Critical Care Medicine·Thomas J RichardsKevin F Gibson
Apr 29, 2015·Journal of Cellular Biochemistry·Anand Krishnan V IyerNeelam Azad
Oct 11, 2011·Cancer Treatment Reviews·Aspasia SoultatiChristos Papadimitriou
Aug 25, 2007·The American Journal of Pathology·Huimin ZhangChin Chiang
May 23, 2015·British Journal for the History of Science·Bill Jenkins
Oct 18, 2012·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Yulin JiaYifang Zhao
Jul 28, 2013·American Journal of Respiratory Cell and Molecular Biology·Heather G LeachMaria Trojanowska

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