Heme oxygenase-1 induction by nitric oxide in RAW 264.7 macrophages is upregulated by a cyclo-oxygenase-2 inhibitor

Unstimulated RAW 264.7 macrophages express negligible heme oxygenase-1 (HO-1) protein but incubation with the nitric oxide (NO) donor spermine nonoate (SPNO) induced HO-1 and weakly cyclo-oxygenase-2 (COX-2) protein. This effect was potentiated by coincubation with the COX-2 selective inhibitor, SC58125. Cells incubated with SPNO showed a strong increase in HO-1 mRNA levels after 4 h with a significant potentiation in the presence of SC58125, which did not modify HO-1 mRNA stability. The induction of HO-1 by NO and its potentiation by anti-inflammatory agents may play a role in inflammatory and immune responses.     

The endothelin system in human and monkey ovaries: in situ gene expression of the different components

The endothelin system is composed of three endothelin isoforms (ET-1, ET-2, and ET-3), the endothelin receptors ETA and ETB, and the endothelin-converting enzyme (ECE). Besides having a major vasoactive role, endothelins have roles in different cell types at a local level. We investigated the presence of the different components of the endothelin system in primate ovaries. Human ovaries and gonadotropin-stimulated monkey ovaries were studied using immunohistochemistry for endothelin, and in situ hybridization with probes for ET-1, ET-2, ET-3, ETA and ETB receptors, and ECE. ET-1 and ETA receptors were detected in endothelial cells and vascular smooth muscle cells, respectively, in stromal vessels adjacent to follicles and corpora lutea. ETB receptors and ET-1 were found in the endothelial cells of capillaries of corpora lutea. ECE was present in internal theca cells of secondary, de Graaf, atretic follicles, and in luteinized granulosa cells of the corpora lutea. The endothelin system components are present in or around the follicles of human and monkey ovaries. Although the components are not expressed in the same cell types, they are synthesized, mainly in follicles, by cells that are in close proximity. Thus, the endothelin system could act in a paracrine manner. ECE expression in steroid-producing cells changes its compartmentalization during follicle maturation.     

Involvement of Ca2+ channels in endothelin-1-induced MAP kinase phosphorylation, myosin light chain phosphorylation and contraction in rabbit iris sphincter smooth muscle

The purpose of the present study was to investigate the role and type of Ca2+ channels involved in the stimulatory effects of endothelin-1 (ET-1) on the Ca2+-dependent functional responses, p42/p44 MAP kinase phosphorylation, 20-kDa myosin light chain (MLC) phosphorylation and contraction, in rabbit iris sphincter, a nonvascular smooth muscle. ET-1 induced inositol phosphates production, MAP kinase phosphorylation, MLC phosphorylation (MLC20-P plus MLC20-2P) and contraction in a concentration-dependent manner with EC50 values of 71, 8, 6 and 25 nM, respectively. ET-1-induced MAP kinase phosphorylation, MLC phosphorylation and contraction were not significantly affected by nifedipine (1-60 microM), an L-type Ca2+ channel blocker, or by LOE 908 (1-100 microM), a blocker of Ca2+-permeable nonselective cation channels. However, SKF96365, a receptor-operated Ca2+ channel (ROCC) blocker, inhibited MAP kinase phosphorylation, MLC phosphorylation and contraction in a concentration-dependent manner with IC50 values of 28, 30 and 42 microM, respectively. 2-APB, a store-operated Ca2+ channel (SOCC) blocker, inhibited ET-1-induced MLC phosphorylation and contraction in a concentration-dependent manner with IC50 values of 12.7 and 19 microM, respectively, but was without effect on MAP kinase phosphorylation. The combined effects of submaximal concentrations of SKF96365 and 2-APB on ET-1-induced MLC phosphorylation and contraction were not additive, implying that their inhibitory actions could be mediated through a common Ca2+ entry channel. PD98059, a MAP kinase inhibitor, had no effect on ET-1-induced MLC phosphorylation and contraction, suggesting that these ET-1 effects in the rabbit iris muscle are MAP kinase-independent. In conclusion, the present study demonstrated for the first time that in rabbit iris sphincter (a) ET-1, through the ETA receptor, stimulates MAP kinase phosphorylation, MLC phosphorylation and contraction in a concentration-dependent manner, (b) that these Ca2+-dependent functional responses are not significantly affected by nifedipine or LOE908, and (c) that ET-1-induced MLC phosphorylation and contraction are inhibited by SKF96365 and 2-APB, suggesting that these effects are mainly due to store- and/or receptor Ca2+ entry.     

Temperament and character in cross-cultural comparisons between Swedish and Iranian people and Iranian refugees in Sweden--personality in transition?

The aim of the study was a cross-cultural comparison of personality traits between individuals from two very different cultures and refugees who resettled several years before from one to the other. Four hundred forty four Swedish individuals of the normal population; and 100 Iranian refugees in Sweden, and a group of 335 individuals from Tehran, capital of Iran, were investigated by means of the Temperament and Character Inventory, a questionnaire to assess temperament and character Iranians are those that are most frequently correctly classified followed by the Swedish based on temperament scores by means of a Discriminance analyses. Iranian refugees in Sweden were classified to about 50 per cent as Swedish and to slightly more then one-third as Iranians. Especially concerning character, 4 per cent only could be correctly classified as refugees. The results give some perspective on the adaptation process and personality changes in refugees several years after resettlement in another country with a complete different culture.     

Diterpenes from the leaves of Croton zambesicus

Two new trachylobane- and one isopimarane-type diterpenoids: ent-18-hydroxy-trachyloban-3-one; ent-trachyloban-3-one; isopimara-7,15-dien-3beta-ol, were isolated from the leaves of Croton zambesicus, together with trans-phytol, beta-sitosterol, alpha-amyrin and stigmasterol. The structures were determined by extensive NMR techniques and X-ray analysis. The cytotoxicity of these compounds has been evaluated on cancer and non-cancer cell-lines.     

Tc1/Tc2 ratio in the inflammatory process in patients with Behçet's disease

BACKGROUND: Peripheral blood CD8+ T cells expressing interferon gamma and interleukin-4 (IL-4), and lacking CD28 molecules, were responsible for the dynamic interplay between peripheral blood and inflammatory sites. INTRODUCTION: The aim of the current study was to define in Behçet''s disease (BD), CD8+ T-cell subsets using CD28 and CD11b monoclonal antibodies, and the characterization of the Tc1/Tc2 ratio and perforin expression. METHODS: Flow cytometry was used for intracytoplasmic cytokines and perforin expression. Effector cells were investigated by adhesion of CD8+ T cells to human microvascular endothelial cells and by chemotaxis using beta-chemokine. RESULTS: Interferon-gamma-producing CD8+ T cells in active and remission BD patients were increased, which induce a significant increase of the Tc1:Tc2 ratio in BD. CD8(+)CD28(-)CD11b+ T cells were found to be more expanded in BD patients than in age-matched healthy controls. The expression of CD11b molecules in active BD allowed to CD8(+)CD28+/CD8(+)CD28- subsets to adhere to human microvascular endothelial cells, with more efficiency in BD. Using MIP-1alpha, we observed that the migratory process of CD28(-)CD11b(+) is more important in BD. CD28(-)CD11b+ exhibited an increased perforin expression in BD patients. CONCLUSION: Taken together these results suggest the presence of immune activation, probably in response to a profound inflammation affecting BD patients. The physiopathological significance of these results were toward autoimmune diseases and/or infectious process.     

Serine protease inhibitors modulate chemotactic cytokine production by human lung fibroblasts in vitro

Chemotactic chemokines can be released from lung fibroblasts in response to interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. An imbalance between proteases and antiproteases has been observed at inflammatory sites, and, therefore, protease inhibitors might modulate fibroblast release of chemotactic cytokines. To test this hypothesis, serine protease inhibitors (FK-706, alpha(1)-antitrypsin, or N(alpha)-p-tosyl-L-lysine chloromethyl ketone) were evaluated for their capacity to attenuate the release of neutrophil chemotactic activity (NCA) or monocyte chemotactic activity (MCA) from human fetal lung fibroblasts (HFL-1). Similarly, the release of the chemoattractants IL-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, macrophage colony-stimulating factor, and granulocyte/macrophage colony-stimulating factor, from HFL-1, were evaluated in response to IL-1beta and TNF-alpha. NCA, MCA, and chemotactic cytokines were attenuated by FK-706. However, matrix metalloproteinase inhibitors were without effect, and cysteine protease inhibitors only slightly attenuated chemotactic or cytokine release. These data suggest that IL-1beta and TNF-alpha may stimulate lung fibroblasts to release NCA and MCA by a protease-dependent mechanism and that serine protease inhibitors may attenuate the release.     

Break of neonatal Th1 tolerance and exacerbation of experimental allergic encephalomyelitis by interference with B7 costimulation

Ig-PLP1 is an Ig chimera expressing proteolipid protein-1 (PLP1) peptide corresponding to aa residues 139-151 of PLP. Newborn mice given Ig-PLP1 in saline on the day of birth and challenged 7 wk later with PLP1 peptide in CFA develop an organ-specific neonatal immunity that confers resistance against experimental allergic encephalomyelitis. The T cell responses in these animals comprise Th2 cells in the lymph node and anergic Th1 lymphocytes in the spleen. Intriguingly, the anergic splenic T cells, although nonproliferative and unable to produce IFN-gamma or IL-4, secrete significant amounts of IL-2. In this work, studies were performed to determine whether costimulation through B7 molecules plays any role in the unusual form of splenic Th1 anergy. The results show that engagement of either B7.1 or B7.2 with anti-B7 Abs during induction of EAE in adult mice that were neonatally tolerized with Ig-PLP1 restores and exacerbates disease severity. At the cellular level, the anergic splenic T cells regain the ability to proliferate and produce IFN-gamma when stimulated with Ag in the presence of either anti-B7.1 or anti-B7.2 Ab. However, such restoration was abolished when both B7.1 and B7.2 molecules were engaged simultaneously, indicating that costimulation is necessary for reactivation. Surprisingly, both anti-B7.1 and anti-B7.2 Abs triggered splenic dendritic cells to produce IL-12, a key cytokine required for restoration of the anergic T cells. Thus, recovery from neonatally induced T cell anergy requires B7 molecules to serve double functions, namely, costimulation and induction of cytokine production by APCs.