Hori M, Kita M, Torihashi S, Miyamoto S, Won K J, Sato K, Ozaki H, Karaki H
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Am J Physiol Gastrointest Liver Physiol. 2001 May;280(5):G930-8. doi: 10.1152/ajpgi.2001.280.5.G930.
We investigated the effect of lipopolysaccharide (LPS) on the induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in muscularis resident macrophages of rat intestine in situ. When the tissue was incubated with LPS for 4 h, mRNA levels of iNOS and COX-2 were increased. The majority of iNOS and COX-2 proteins appeared to be localized to the dense network of muscularis resident macrophages immunoreactive to ED2. LPS treatment also increased the production of nitric oxide (NO), PGE(2), and PGI(2). The increased expression of iNOS mRNA by LPS was suppressed by indomethacin but not by N(G)-monomethyl-L-arginine (L-NMMA). The increased expression of COX-2 mRNA by LPS was affected neither by indomethacin nor by L-NMMA. Muscle contractility stimulated by 3 microM carbachol was significantly inhibited in the LPS-treated muscle, which was restored by treatment of the tissue with L-NMMA, aminoguanidine, indomethacin, or NS-398. Together, these findings show that LPS increases iNOS expression and stimulates NO production in muscularis resident macrophages to inhibit smooth muscle contraction. LPS-induced iNOS gene expression may be mediated by autocrine regulation of PGs through the induction of COX-2 gene expression.
我们研究了脂多糖（LPS）对大鼠肠道肌层驻留巨噬细胞中诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）诱导作用的影响。当组织与LPS孵育4小时后，iNOS和COX-2的mRNA水平升高。大多数iNOS和COX-2蛋白似乎定位于对ED2免疫反应的肌层驻留巨噬细胞的致密网络中。LPS处理还增加了一氧化氮（NO）、前列腺素E2（PGE2）和前列环素（PGI2）的产生。LPS诱导的iNOS mRNA表达增加被吲哚美辛抑制，但不被N-甲基-L-精氨酸（L-NMMA）抑制。LPS诱导的COX-2 mRNA表达增加既不受吲哚美辛影响，也不受L-NMMA影响。在LPS处理的肌肉中，3 microM卡巴胆碱刺激的肌肉收缩力明显受到抑制，用L-NMMA、氨基胍、吲哚美辛或NS-398处理组织可使其恢复。总之，这些发现表明，LPS增加iNOS表达并刺激肌层驻留巨噬细胞中NO的产生，从而抑制平滑肌收缩。LPS诱导的iNOS基因表达可能通过诱导COX-2基因表达由PGs的自分泌调节介导。
