No abstract

No abstract

Activated pancreatic stellate cells (PSCs) have recently been implicated in the pathogenesis of pancreatic fibrosis and inflammation. However, the signal transduction pathways in PSCs remain largely unknown. We examined the role of p38 mitogen-activated protein (MAP) kinase in the activation of PSCs. PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype. Activation of p38 MAP kinase was determined by Western blotting using anti-phosphospecific antibody. The effects of two p38 MAP kinase inhibitors, 4-(4-flurophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole (SB203580) and 4-(4-flurophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole (SB202190), on the parameters of PSC activation, including proliferation, expression of alpha-smooth muscle actin, alpha1(I) procollagen, and prolyl 4-hydroxylase (alpha) genes, and monocyte chemoattractant protein-1 production were evaluated. Interleukin-1beta and platelet-derived growth factor-BB activated p38 MAP kinase. Platelet-derived growth factor-induced PSC proliferation was inhibited by SB203580 and SB202190. These reagents decreased alpha-smooth muscle actin protein expression, and alpha1(I) procollagen and prolyl 4-hydroxylase (alpha) mRNA levels. Treatment with these p38 MAP kinase inhibitors also resulted in inhibition of monocyte chemoattractant protein-1 expression. In addition, SB203580 inhibited spontaneous activation of freshly isolated PSCs in culture on plastic. Thus, inhibition of p38 MAP kinase modulated profibrogenic and proinflammatory actions in PSCs, implying a potential application of p38 MAP kinase inhibitors for the treatment of pancreatic fibrosis and inflammation.

The preparation and structural characterization of the novel polyoxoanion [(alpha-1,2,3-P(2)W(15)Ti(3)O(62))(4)[mu(3)-Ti(OH)(3)](4)Cl](45-) (1 a; abbreviated to [TiO(6)](16); FW approximately 16 000) which consists of four tri-Ti(IV)-1,2,3-substituted alpha-Dawson substructures, four Ti(OH)(3) bridging groups, and one encapsulated Cl(-) ion, are described. A water-soluble, all-inorganic composition compound of the tetrameric Ti-O-Ti-bridged anhydride form, Na(x)H(45-x)[1 a].y H(2)O (1; x=16-19, y=60-70), which was afforded by the reaction of the tri-lacunary Dawson polyoxotungstate Na(12)[B-alpha-P(2)W(15)O(56)].19 H(2)O with an excess of TiCl(4) in aqueous solution, was obtained as analytically pure, homogeneous colorless crystals. Single-crystal X-ray structure analysis revealed that 1 a was an inorganic, giant "tetrapod"-shaped molecule (inscribed to a sphere with a diameter of approximately 32 A) with approximately T(d) symmetry, in which the 16 edge- and/or corner-shared TiO(6) octahedra were contained. This number of TiO(6) octahedra was larger than that found in other titanium(IV)-substituted polyoxotungstates. Complex 1 was characterized by complete elemental analysis, TG/DTA, FTIR, UV/Vis absorption, and solution ((31)P and (183)W) NMR spectroscopy. The longest wavelength band in the UV/Vis absorption spectra of 1 in water was attributed to the O-->Ti(IV) ligand-to-metal charge-transfer (LMCT) transition: the wavelength of the LMCT band increased linearly as the number of TiO(6) octahedra contained in the Keggin and Dawson polyoxoanions increased. The Ti(n) chromophores formed in the Keggin and Dawson polyoxotungstates are water-soluble analogues of solid TiO(2) or SrTiO(3) as light-semiconductors and photocatalysts.

In acute pancreatitis, the low percentage of HLA-DR-expressing cells in the monocyte population is a reliable predictor of the development of sepsis. Monitoring of monocyte HLA-DR expression may be a useful marker for identifying the patients who are at high risk of sepsis in acute pancreatitis.