Osteopontin (OPN) is a secreted phosphoprotein that is constitutively expressed in the normal kidney and is induced by various experimental and pathologic conditions. Several possible functions of OPN have been suggested, however the mechanism and significance of OPN expression are still uncertain. Since high salt concentration or salt crystal have been known to enhance OPN expression in intact kidney or cultured renal cells, in the present study we examined whether or not a low salt condition had an effect on OPN expression in the kidney. Adult male Sprague-Dawley rats were fed either a normal sodium or a sodium deficient diet for 1 week. Kidneys were processed for in situ hybridization using a digoxigenin-labeled riboprobe and for immunohistochemistry using antibodies to OPN, renin, and Na-K-ATPase. In rats fed a normal sodium diet, OPN mRNA and protein were expressed only in the descending thin limbs of Henle's loop (DTL) and in the papillary and pelvic surface epithelium (PSE). In rats fed a sodium deficient diet, there was a marked decrease in OPN immunoreactivity in the DTL, but no changes in PSE. In contrast, no changes were observed in OPN mRNA expression in the DTL by in situ hybridization, indicating that decreased OPN protein expression was a result of translational regulation. As expected, rats fed a sodium deficient diet were associated with increased immunoreactivity for Na-K-ATPase and renin compatible with activation of the renin-angiotensin system. These results suggest that dietary sodium may be involved in the regulation of OPN expression in the DTL of the rat kidney.
Animal ; Diet, Sodium-Restricted* ; Immunohistochemistry ; In Situ Hybridization ; Kidney/metabolism* ; Male ; Na(+)-K(+)-Exchanging ATPase/metabolism ; Rats ; Rats, Sprague-Dawley ; Renin/metabolism ; Sialoglycoproteins/metabolism ; Sialoglycoproteins/antagonists & inhibitors* ; Sodium/deficiency*

BACKGROUND: The human immune response to Mycobacterium tuberculosis is mediated by macrophages and T-lymphocytes. The alveolar macrophage phagocyting mycobacterium produces interleukin (IL) -1 as an inflammatory mediator, and IL-8 as a cytokine for leukocyte recruitment and granuloma formation. Interleukin-1 receptor antagonist (IL-1ra) is an internal antagonist of IL-1. METHODS: Plasma levels of IL-1ra and IL-8 and other serologic markers were measured in 18 patients with active tuberculosis before treatment and after 2 months and 6 months of treatment. RESULTS: During treatment with antituberculous medication, patients showed significant changes in hemoglobin, hematocrit, white blood cells (WBC), platelet, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin and plasma IL-1ra. After 2 months of treatment, ESR and CRP diminished significantly; after 6 months, hemoglobin increased while WBC, platelet, ESR, CRP and ferritin decreased significantly compared to their pre-treatment levels. There were two groups: patients with delayed therapeutic responses, and patients with early responses. At each point of observation, the former group of patients showed lower body weight and lower levels of hemoglobin and hematocrit, and higher levels of WBC, platelet, ESR, IL-8 and IL-1ra than the latter group. During the course of the treatment, we observed considerable differences in body weight, body mass index, hemoglobin, hematocrit, WBC and platelet counts, ESR, CRP and ferritin in both the early-response and delayed-response groups. CONCLUSION: We believe that the plasma concentrations of IL-1ra and IL-8, which showed different peaks during the course of treatment, reflected their different functions and patterns of secretion. Moreover the concentrations did not seem as sensitive as other inflammatory markers to evaluate disease activity during antituberculosis treatment. However, IL-1ra can be considered a marker for disease activity and response to treatment.
Adult ; Aged ; Aged, 80 and over ; Antitubercular Agents/therapeutic use ; Biological Markers/*blood ; C-Reactive Protein/analysis ; Comparative Study ; Female ; Human ; Interleukin-8/*blood ; Male ; Middle Aged ; Receptors, Interleukin-1/*antagonists & inhibitors ; Sialoglycoproteins/*blood ; Tuberculosis, Pulmonary/*blood/*drug therapy

AIMTo study the effects of human recombinant interleukin-1 receptor antagonist (IL-1ra) on isolated trachea smooth muscle (TSM) of the guinea pig.

METHODSChanges of the tension of isolated trachea were measured by force-displacement transducer and MedLab recording system in vitro.

RESULTSIL-1ra showed direct relaxed effect on TSM in normal and ovalbumin sensitized guinea pig. The EC50 values were 8.06 x 10(-8) and 5.88 x 10(-7) mol.L-1 respectively. IL-1ra (1 x 10(-7)-1 x 10(-5) mol.L-1) concentration-dependently inhibited the contraction of TSM induced by 1 x 10(-3) mol.L-1 histamine (His), 1 x 10(-3) mol.L-1 acetylcholine (ACh) and 1 x 10(-6) mol.L-1 5-hydroxytryptamine (5-HT) (P < 0.05 or 0.01). When IL-1ra was given in advance, the contractile actions of His, ACh and 5-HT were antagonized by IL-1ra (1 x 10(-7)-1 x 10(-5) mol.L-1), the pD'2 value for His was 6.6 +/- 0.3. However, the contractile action of ACh was enhanced by IL-1ra at low concentration of 1 x 10(-9)-1 x 10(-8) mol.L-1. IL-1ra significantly prevented and inhibited the contraction of sensitized TSM induced by antigen ovalbumin, the IC50 value was 4.48 x 10(-7) mol.L-1.

CONCLUSIONThe results indicate that IL-1ra, within certain concentration, can relax the normal, contracted and sensitized ISM of the guinea pig in vitro.

Animals ; Female ; Guinea Pigs ; In Vitro Techniques ; Interleukin 1 Receptor Antagonist Protein ; Male ; Muscle Contraction ; drug effects ; Muscle, Smooth ; drug effects ; Receptors, Interleukin-1 ; antagonists & inhibitors ; Recombinant Proteins ; pharmacology ; Sialoglycoproteins ; pharmacology ; Trachea ; cytology

AIMTo evaluate the effect of interleukin-1 receptor antagonist(IL-1ra) on apoptosis and associated mechanism of eosinophil in guinea pig with asthma.

METHODSA model of guinea pig with asthma was established. After inhalation of different concentrations of IL-1ra, asthma was induced in the guinea pig for 8 days, the concentration of eosinophil cationic protein (ECP) in serum and bronchoalveolar lavage fluid (BALF), IL-5 in serum, the eosinophil counts and apoptosis were assayed by radioimmunology, enzyme-linked immunosorbent assay(ELISA), fluoromicroscope and light microscope.

RESULTSIL-1ra indirectly decreased the level of IL-5 in serum, improved the apoptosis of eosinophil(EOS) in lung, then decreased the level of ECP in serum and BALF.

CONCLUSIONInhalation of nebulized IL-1ra showed protective effect against asthma through change of the activity and infiltration of EOS in lung.

Animals ; Apoptosis ; Asthma ; blood ; chemically induced ; pathology ; Blood Proteins ; metabolism ; Bronchoalveolar Lavage Fluid ; chemistry ; Eosinophil Granule Proteins ; Eosinophils ; drug effects ; pathology ; Female ; Guinea Pigs ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-5 ; blood ; Leukocyte Count ; Male ; Ovalbumin ; Random Allocation ; Receptors, Interleukin-1 ; antagonists & inhibitors ; Ribonucleases ; blood ; metabolism ; Sialoglycoproteins ; pharmacology