Modulation of inflammatory response by pentoxifylline is independent of heme oxygenase-1 pathway

• Published in: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society Vol. 60; no. 2; p. 3
• Main Authors: Taha, H, Grochot-Przeczek, A, Was, H, Kotlinowski, J, Kozakowska, M, Marek, A, Skrzypek, K, Lackowska, B, Balcerczyk, A, Mustafa, S, Dulak, J, Jozkowicz, A
• Format: Journal Article
• Language: English
• Published: Poland 01-06-2009
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Cell Line; Dose-Response Relationship, Drug; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelium, Vascular - cytology; Endotoxemia - drug therapy; Endotoxemia - metabolism; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Humans; Lipopolysaccharides - pharmacology; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes - drug effects; Monocytes - metabolism; Pentoxifylline - pharmacology; Phosphodiesterase Inhibitors - pharmacology; Polymorphism, Genetic; Signal Transduction - drug effects; Tumor Necrosis Factor-alpha - biosynthesis; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 1899-1505

It was reported that some effects of pentoxifylline (PTX) are mediated by heme oxygenase-1 (HO-1) induction. We investigated the role of HO-1 in anti-inflammatory activity of PTX.
Experiments were performed in human and murine monocytes and endothelial cells and in HO-1 deficient mice.
PTX dose-dependently decreased expression of HO-1 in cell lines studied. As expected, PTX reduced also production of TNF. This effect was independent of HO-1 activity, as demonstrated in cells treated with HO-1 activators and inhibitors or in cells overexpressing HO-1. Moreover, inhibition of TNF was the same in human endothelial cells of different HO-1 genotypes, showing that PTX is similarly efficient in carriers of more and less active HO-1 promoter variants. In mice, PTX did not influence HO-1 expression, as measured in liver, kidney, spleen, heart, and skin. Accordingly, the response of PTX treated animals to LPS was the same in wild type and HO-1 deficient mice. PTX to a similar extent increased influx of leukocyte into peritoneal cavity, decreased production of TNF and reduced expression of VCAM-1 in vascular intima.
PTX inhibits production of TNF and may decrease inflammatory reaction both in vitro and in vivo, but these effects are independent of HO-1.