Human CMV infection induces 5-lipoxygenase expression and leukotriene B4 production in vascular smooth muscle cells.
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 LTB(4). 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.
Qiu
Hong
H
Department of Medical Biochemistry and Biophysics, Division of Chemistry II, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Strååt
Klas
K
Rahbar
Afsar
A
Wan
Min
M
Söderberg-Nauclér
Cecilia
C
Haeggström
Jesper Z
JZ
D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis*; D002478:Cells, Cultured; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D005347:Fibroblasts / Q000821:virology; D005786:Gene Expression Regulation; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007249:Inflammation; D007975:Leukotriene B4 / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000821:virology; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000821:virology
D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase