RESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) affects up to 10% of adults globally, and its complications can mask the risk of gastrointestinal bleeding or malignancy. METHODS: Our study enrolled 633 endoscopic patients stratified according to T2DM presence (4:1 ratio in favor of the control group). RESULTS: T2DM patients referred for endoscopy experienced lower prevalence of epigastric pain and heartburn (OR = 0.637/OR = 0.346, p < 0.05). Often being anemic (OR = 2.23, p < 0.001), they had significantly lower hemoglobin (p = 0.001) and serum iron (p = 0.02), but serum cholesterol was higher in non-diabetics. Ulcers, erosions and mucosal hemorrhages were comparable between groups (p < 0.05), although low-dose aspirin use was more prevalent in diabetics (p = 0.000, OR = 2.34). T2DM was associated with the increased frequency of antro-corporal active gastritis (OR = 1.451/OR 1.501), with smokers presenting a higher frequency of active H. pylori infection (OR = 3.37). T2DM predicted anemia (adjusted OR = 1.70) and the absence of gastroesophageal reflux symptoms (adjusted OR = 0.37), but not active H. pylori gastritis or premalignant lesions. CONCLUSION: In an endoscopic population, patients with T2DM had lower hemoglobin and serum iron levels. There was an inverse correlation between T2DM and heartburn. H. pylori gastritis and premalignant lesions occurred more frequently in diabetic patients (predominantly pangastritis) before adjusting for age or associated comorbidities, with smoking increasing the risk for active infection.
RESUMO
Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has been implicated in the pathogenesis of inflammatory disorders such as infection, sepsis, and autoimmune disease. MIF exists preformed in cytoplasmic pools and exhibits an intrinsic tautomerase and oxidoreductase activity. MIF levels are elevated in the serum of animals and patients with infection or different inflammatory disorders. To elucidate how MIF actions are controlled, we searched for endogenous MIF-interacting proteins with the potential to interfere with key MIF functions. Using in vivo biotin-tagging and endogenous co-immunoprecipitation, the ribosomal protein S19 (RPS19) was identified as a novel MIF binding partner. Surface plasmon resonance and pulldown experiments with wild type and mutant MIF revealed a direct physical interaction of the two proteins (K(D) = 1.3 x 10(-6) m). As RPS19 is released in inflammatory lesions by apoptotic cells, we explored whether it affects MIF function and inhibits its binding to receptors CD74 and CXCR2. Low doses of RPS19 were found to strongly inhibit MIF-CD74 interaction. Furthermore, RPS19 significantly compromised CXCR2-dependent MIF-triggered adhesion of monocytes to endothelial cells under flow conditions. We, therefore, propose that RPS19 acts as an extracellular negative regulator of MIF.
Assuntos
Células Endoteliais/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Monócitos/metabolismo , Receptores de Interleucina-8B/metabolismo , Proteínas Ribossômicas/metabolismo , Animais , Apoptose/genética , Doenças Autoimunes/genética , Doenças Autoimunes/metabolismo , Adesão Celular/genética , Humanos , Inflamação/genética , Inflamação/metabolismo , Fatores Inibidores da Migração de Macrófagos/genética , Camundongos , Mutação , Células NIH 3T3 , Oxirredutases/genética , Oxirredutases/metabolismo , Ligação Proteica/genética , Ratos , Receptores de Interleucina-8B/agonistas , Receptores de Interleucina-8B/genética , Proteínas Ribossômicas/genética , Sepse/genética , Sepse/metabolismo , Ressonância de Plasmônio de SuperfícieRESUMO
In ciliated airway epithelial cells endothelial nitric oxide synthase as well as several other membrane bound proteins are located in the apical cell pole. To date, mechanisms that serve to target and to keep these proteins in this region are unknown. Endothelial nitric oxide synthase is known to target to caveolae by interaction with caveolin-1 or caveolin-3. Since caveolin-1 is found only in a subpopulation of ciliated cells at the basolateral cell membrane, we examined if caveolin-3 could be responsible for the apical localization of endothelial nitric oxide synthase in ciliated cells. We used real-time RT-PCR, laser-assisted microdissection, Western blotting and double-labeling immunohistochemistry to examine the presence of caveolin-3 in the airway epithelium of the rat. Indeed, we found caveolin-3-mRNA as well as protein in ciliated cells throughout the trachea and the bronchial tree. Caveolin-3-immunoreactivity was confined to the apical region and was colocalized with endothelial nitric oxide synthase and the high affinity choline transporter in a compartment distinct from the plasma membrane at the light microscopic level. No caveolae were found in the apical plasma membrane of ciliated cells but a tubulovesicular network was present in the apical region that reached up to the basal bodies of the cilia and was in close contact with mitochondria. Co-immunoprecipitation of caveolin-3 with endothelial nitric oxide synthase verified that both proteins interact in airway ciliated cells. These findings indicate that caveolin-3 is responsible to keep endothelial nitric oxide synthase in a membrane compartment in the apical region of ciliated cells.