BACKGROUND & AIMS Bone morphogenetic protein (BMP)4 is a mesenchymal peptide that regulates cells of the gastric epithelium. We investigated whether BMP signaling pathways affect gastric inflammation after bacterial infection of mice. METHODS We studied transgenic mice that express either the BMP inhibitor noggin or the β- galactosidase gene under the control of a BMP-responsive element and BMP4βgal/+ mice. Gastric inflammation was induced by infection of mice with either Helicobacter pylori or Helicobacter felis. Eight to 12 weeks after inoculation, gastric tissue samples were collected and immunohistochemical, quantitative, reverse-transcription polymerase chain reaction and immunoblot analyses were performed. We used enzyme-linked immunosorbent assays to measure cytokine levels in supernatants from cultures of mouse splenocytes and dendritic cells, as well as from human gastric epithelial cells (AGS cell line). We also measured the effects of BMP-2, BMP-4, BMP-7, and the BMP inhibitor LDN-193189 on the expression of interleukin (IL)8 messenger RNA by AGS cells and primary cultures of canine parietal and mucus cells. The effect of BMP-4 on NFkB activation in parietal and AGS cells was examined by immunoblot and luciferase assays. RESULTS Transgenic expression of noggin in mice increased H pylori– or H felis–induced inflammation and epithelial cell proliferation, accelerated the development of dysplasia, and increased expression of the signal transducer and activator of transcription 3 and activation-induced cytidine deaminase. BMP-4 was expressed in mesenchymal cells that expressed α-smooth muscle actin and activated BMP signaling pathways in the gastric epithelium. Neither BMP-4 expression nor BMP signaling were detected in immune cells of C57BL/6, BRE–β-galactosidase, or BMP-4βgal/+ mice. Incubation of dendritic cells or splenocytes with BMP-4 did not affect lipopolysaccharide-stimulated production of cytokines. BMP-4, BMP-2, and BMP-7 inhibited basal and tumor necrosis factor α–stimulated expression of IL8 in canine gastric epithelial cells. LDN-193189 prevented BMP4-mediated inhibition of basal and tumor necrosis factor α–stimulated expression of IL8 in AGS cells. BMP-4 had no effect on TNFα-stimulated phosphorylation and degradation of IκBα, or on TNFα induction of a NFκβ reporter gene. CONCLUSIONS BMP signaling reduces inflammation and inhibits dysplastic changes in the gastric mucosa after infection of mice with H pylori or H felis.
A fraction of the heavily reddened quasars require a reddening curve which is even steeper than that of the Small Magellanic Cloud. In this paper, we thoroughly characterize the anomalously steep reddening law in quasars, via an exceptional example observed in IRAS 14026+4341. By comparing the observed spectrum to the quasar composite spectrum, we derive a reddening curve in the rest-frame wavelength range of 1200Å-10000Å. It is featured with a steep rise at wavelengths shorter than 3000Å, but no significant reddening at longer wavelengths. The absence of dust reddening in optical continuum is confirmed by the normal broad-line Balmer decrement (the Hα/Hβ ratio) in IRAS 14026+4341. The anomalous reddening curve can be satisfactorily reproduced by a dust model containing silicate grains in a power-law size distribution, dn(a)/da ∝ a −1.4 , truncated at a maximum size a max = 70 nm. The unusual size distribution may be caused by the destruction of large "stardust" grains by quasar activities or a different dust formation mechanism (i.e., the in situ formation of dust grains in quasar outflows). It is also possible that the analogies of the dust grains observed toward the Galactic center is responsible for the steep reddening curve. In addition, we find that IRAS 14026+4341 is a weak emission-line quasar (i.e., PHL 1811 analogies) with heavy dust reddening and blueshifted broad absorption lines.
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