13 research outputs found
Endogenous annexin A1 counter-regulates bleomycin-induced lung fibrosis
PMCID: PMC3212807This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Biphasic Modulation of NOS Expression, Protein and Nitrite Products by Hydroxocobalamin Underlies Its Protective Effect in Endotoxemic Shock: Downstream Regulation of COX-2, IL-1 beta, TNF-alpha, IL-6, and HMGB1 Expression
Background. NOS/âąNO inhibitors are potential therapeutics for sepsis, yet they increase clinical mortality. However, there has been no in vivo investigation of the (in vitro) âąNO scavenger, cobalaminâs (Cbl) endogenous effects on NOS/âąNO/inflammatory mediators during the immune response to sepsis. Methods. We used quantitative polymerase chain reaction (qPCR), ELISA, Western blot, and NOS Griess assays, in a C57BL/6 mouse, acute endotoxaemia model. Results. During the immune response, pro-inflammatory phase, parenteral hydroxocobalamin (HOCbl) treatment partially inhibits hepatic, but not lung, iNOS mRNA and promotes lung eNOS mRNA, but attenuates the LPS hepatic rise in eNOS mRNA, whilst paradoxically promoting high iNOS/eNOS protein translation, but relatively moderate âąNO production. HOCbl/NOS/âąNO regulation is reciprocally associated with lower 4âh expression of TNF-α, IL-1ÎČ, COX-2, and lower circulating TNF-α, but not IL-6. In resolution, 24âh after LPS, HOCbl completely abrogates a major late mediator of sepsis mortality, high mobility group box 1 (HMGB1) mRNA, inhibits iNOS mRNA, and attenuates LPS-induced hepatic inhibition of eNOS mRNA, whilst showing increased, but still moderate, NOS activity, relative to LPS only. experiments (LPS+D-Galactosamine) HOCbl afforded significant, dose-dependent protection in
mice Conclusions. HOCbl produces a complex, time- and organ-dependent, selective regulation of NOS/âąNO during endotoxaemia, corollary regulation of downstream inflammatory mediators, and increased survival. This merits clinical evaluation
The impact of endogenous annexin A1 on glucocorticoid control of in ammatory arthritis
This work was supported by a Wellcome Trust (UK) project grant 083551. SMO is funded by Fundação de Amparo Ă Pesquisa do Estado de SĂŁo Paulo â FAPESP (Grant 2011/00128-1) and Conselho Nacional de Desenvolvimento CientĂfico e TecnolĂłgico â CNPq (Grant 302768/2010-6)
Flavonoids Bearing an O-arabinofuranosyl-(1 -> 3)-rhamnoside Moiety from Cladocolea micrantha: Inhibitory Effect on Human Melanoma Cells
Eleven known triterpenes (alpha-amyrin, beta-amyrin, lupeol, and their respective acetates, 3-O-acetyl derivatives of betulinic, oleanolic, and ursolic acids, cycloartenol, and tirucall-7,24-dicnol), two new flavonols presenting an uncommon interglycosidic O-[1 -> 3) linkage (kaempferol 3-O-alpha-L-arabinofuranosyl-(1 -> 3)-alpha-L-rhamnoside and quercetin 3-O-alpha-L-arabinofuranosyl-(1 -> 3)-alpha-L-rhamnoside), beta-sitosterol, stigmasterol, quercetin, and gallic acid were isolated from the Amazonian medicinal mistletoe, Cladocolea micrantha Kuijt (Loranthaceae). Their structures were established by spectral methods and eventual chromatographic comparisons. The quercetin derivative was not cytotoxic to MV3 human melanoma cells, but was able, when administered at 1 mu g/mL, to promote a twofold inhibition of the migration of the cells through the transwell system when compared with paclitaxel at 5 mu M.71013111314Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)FAPERJ Grant [E-26/110.032/2011