Human CMV infection induces 5-lipoxygenase expression and leukotriene B4 production in vascular smooth muscle cells

H Qiu, K Strååt, A Rahbar, M Wan… - The Journal of …, 2008 - rupress.org
H Qiu, K Strååt, A Rahbar, M Wan, C Söderberg-Nauclér, JZ Haeggström
The Journal of experimental medicine, 2008rupress.org
Leukotrienes (LTs) are powerful proinflammatory lipid mediators that may play a central role
in cardiovascular diseases, including arteriosclerosis, myocardial infarction, and stroke.
Owing to restricted expression of 5-lipoxygenase (5-LO), the enzyme required for their
synthesis, LTs are almost exclusively produced by myeloid cells. Here, we report that human
cytomegalovirus (HCMV) infection of human vascular smooth muscle cells (SMCs)
increases 5-LO mRNA levels by up to 170-fold in a dose-and time-dependent manner …
Leukotrienes (LTs) are powerful proinflammatory lipid mediators that may play a central role in cardiovascular diseases, including arteriosclerosis, myocardial infarction, and stroke. Owing to restricted expression of 5-lipoxygenase (5-LO), the enzyme required for their synthesis, LTs are almost exclusively produced by myeloid cells. Here, we report that human cytomegalovirus (HCMV) infection of human vascular smooth muscle cells (SMCs) increases 5-LO mRNA levels by up to 170-fold in a dose- and time-dependent manner. Infected cells expressed 5-LO protein, as shown by immunohistochemistry, enabling them to synthesize bioactive LTB4. HCMV-infected vascular SMCs expressing 5-LO protein were readily detected in tissue samples from CMV-infected patients with inflammatory bowel disease or AIDS. Thus, pathogen-induced LT production in HCMV-infected tissues may contribute to local inflammation, consistent with the ability of HCMV to control cellular and immunological functions. HCMV-induced LT biosynthesis in SMCs offers a molecular mechanism to explain HCMV-induced pathogenesis in inflammatory diseases.
rupress.org