Odoux C, Crestani B, Lebrun G, Rolland C, Aubin P, Fournier T, Fiet J, Aubier M
Institut National de la Santé et de la Recherche Médicale U408, Faculté Xavier Bichat, Paris, France.
Am J Physiol. 1997 Jul;273(1 Pt 1):L193-200. doi: 10.1152/ajplung.1997.273.1.L193.
The aim of this study was to characterize the effect of alveolar macrophage (AM) secretory products on endothelin (ET)-1 production by rat alveolar type II (ATII) cells in primary culture. We quantified preproendothelin (ppET)-1 mRNA by Northern blot and ET-1 concentrations in cell supernatants by enzyme-linked immunosorbent assay. Conditioned medium (CM) from rat adherent AM decreased the ppET-1 mRNA levels in ATII cells and reduced ET-1 concentrations in cell culture supernatants. This effect was mediated by interleukin (IL)-1 beta as shown by pretreatment of CM with an anti-IL-1 beta neutralizing antiserum. IL-1 beta effect was dependent on protein synthesis, was partially prevented with indomethacin, and was totally prevented with dexamethasone. Specific inhibition of cyclooxygenase 2 activity completely reversed the effect of IL-1 beta. We conclude that rat AM inhibit ET-1 production by rat ATII cells in vitro through IL-1 beta secretion. The IL-1 beta-mediated inhibition is dependent on the cyclooxygenase 2 pathway. Downregulation of ET-1 production by activated AM could limit the intra-alveolar burden of this profibrogenic peptide and thus could prevent fibrosis development.
本研究的目的是确定肺泡巨噬细胞（AM）分泌产物对原代培养的大鼠肺泡Ⅱ型（ATII）细胞产生内皮素（ET）-1的影响。我们通过Northern印迹法对前内皮素（ppET）-1 mRNA进行定量，并通过酶联免疫吸附测定法对细胞上清液中的ET-1浓度进行定量。来自大鼠贴壁AM的条件培养基（CM）降低了ATII细胞中ppET-1 mRNA水平，并降低了细胞培养上清液中的ET-1浓度。如用抗IL-1β中和抗血清对CM进行预处理所示，这种作用是由白细胞介素（IL）-1β介导的。IL-1β的作用依赖于蛋白质合成，吲哚美辛可部分阻断其作用，地塞米松可完全阻断其作用。环氧化酶2活性的特异性抑制完全逆转了IL-1β的作用。我们得出结论，大鼠AM在体外通过分泌IL-1β抑制大鼠ATII细胞产生ET-1。IL-1β介导的抑制作用依赖于环氧化酶2途径。活化的AM下调ET-1的产生可能会限制这种促纤维化肽在肺泡内的负荷，从而预防纤维化的发展。
