期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：12
页码：4637-4642
DOI：10.1073/pnas.0407655101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Bacteria stimulate macrophages as part of normal host defense. However, when this response is not limited, vascular smooth muscle may also be activated to express "vasoactive" genes (e.g., cyclooxygenase), leading to vascular collapse and septic shock. In macrophages, Toll-like receptors (TLRs) 4 and 2 transduce responses to Gram-negative and Gram-positive bacteria, respectively. However, the role of these TLRs in sensing bacteria in vascular smooth muscle is unclear. To address this question, we have cultured vascular smooth muscle cells from mice deficient in TLR4 (TLR4-/- mice), mice deficient in TLR2 (TLR2-/- mice), or control mice. Cells cultured from control or TLR2-/- mice, but not from TLR4-/- mice, expressed cyclooxygenase-2 and released increasing levels of prostaglandin E2 after stimulation with whole Escherichia coli bacteria; the combination of IL-1{beta} plus TNF-{alpha} induced cyclooxygenase-2 in cells cultured from all three groups of animals. By contrast, Staphylococcus aureus affected cyclooxygenase-2 expression in two distinct ways. First, S. aureus induced a transient inhibition of cyclooxygenase-2 expression, which was overcome with time, and increased protein expression was noted. The effects of S. aureus on cyclooxygenase-2 expression were TLR2- and not TLR4-dependent. Thus, we show that Gram-positive and Gram-negative bacteria induce cyclooxygenase-2 in vascular smooth muscle with differing temporal profiles but with appropriate TLR2-versus-TLR4 signaling. These data have important implications for our understanding of the innate immune response in vascular cells and how it may impact vascular disease.
