Yano T, Hopkins H A, Hempel S L, Monick M, Hunninghake G W
Department of Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
J Cell Physiol. 1995 Oct;165(1):77-82. doi: 10.1002/jcp.1041650110.
Several studies have shown that interleukin-4 (IL-4) down-regulates synthesis of prostaglandin E2 (PGE2). We evaluated the mechanisms for this suppression in human alveolar macrophages (HAMs). Normal HAMs were obtained from healthy nonsmoking volunteers. The cells either remained unstimulated, or were exposed to 10 micrograms/ml of lipopolysaccharide (LPS) and/or various amounts of IL-4. LPS alone induced the synthesis of large amounts of PGE2 and prostaglandin H synthase-2 (PGHS-2) protein. This effect of LPS was suppressed by increasing amounts of IL-4. Expression of LPS-induced PGHS-2 mRNA was also inhibited by IL-4. In addition, IL-4 inhibited expression of CD14, which is a receptor for LPS bound to the LPS-binding protein (LBP). We conclude that IL-4 down-regulates LPS-induced release of PGE2, by reducing expression of the enzyme, PGHS-2. One potential mechanism for this effect of IL-4 is a reduced expression of CD14, which is the LPS-LBP receptor.
多项研究表明，白细胞介素-4（IL-4）可下调前列腺素E2（PGE2）的合成。我们评估了人类肺泡巨噬细胞（HAMs）中这种抑制作用的机制。正常HAMs取自健康非吸烟志愿者。细胞要么保持未受刺激状态，要么暴露于10微克/毫升的脂多糖（LPS）和/或不同量的IL-4中。单独的LPS可诱导大量PGE2和前列腺素H合酶-2（PGHS-2）蛋白的合成。LPS的这种作用被越来越多的IL-4所抑制。IL-4也抑制LPS诱导的PGHS-2 mRNA的表达。此外，IL-4抑制CD14的表达，CD14是与脂多糖结合蛋白（LBP）结合的LPS的受体。我们得出结论，IL-4通过降低酶PGHS-2的表达来下调LPS诱导的PGE2释放。IL-4产生这种作用的一个潜在机制是作为LPS-LBP受体的CD14表达降低。
