Effect of insulin-like growth factor-1 on promoting healing of skin ulcers in diabetic rats.

To investigate the effect of exogenous insulin-like growth factor-1 (IGF-1) on the healing of skin ulcers in diabetic rats, male Sprague Dawleys (SD) rats with back skin ulcers were selected and divided into control group, model group and IGF-1 treatment group which received different doses of IGF-1 (0.5, 1.0, 1.5, and 2.0mg/L). The results showed that the healing speed of the skin ulcers was significantly affected by IGF-1, which reduced the size of wound (P less than 0.05). The expression of MMP-9 was enhanced while the expression of TIMP-1 was decreased in diabetic rats with skin ulcers. The IGF-1 treatment helped to re¬store the normal expression of both MMP-9 and TIMP-1 in diabetic rats with skin ulcers, and diabetic skin ulcers in the 1.5 mg/L IGF-1 group showed the best healing. Histological examination showed that after 20 days, fibroblasts in the IGF-1 experimental group with an appropriate concentration increased and the numbers of fibroblasts and capillaries were significantly higher than those of the other groups. Moreover, there were obvious wound surface contractions and re-epithelialization, and the new epithelium moved to the center of the wound faster. Therefore, it is concluded that an appropriate concentration of IGF-1 can significantly promote the healing of skin ulcers in diabetic rats.

IL10 rs1800896 polymorphism is associated with liver cirrhosis and chronic hepatitis B.

We conducted a case-control study to assess the role of two IL10 gene polymorphisms (rs1800896 and rs1800872) in susceptibility to liver cirrhosis, and their association with chronic hepatitis B in a Chinese population. A case-control study was designed to investigate the association between functional polymorphisms of IL10 (rs1800896 and rs1800872) and the development of liver cirrhosis. Between March 2012 and March 2014, we recruited 241 patients with liver cirrhosis and 254 controls from Xianyang Central Hospital. Genotyping of IL10 rs1800896 and rs1800872 polymorphisms was carried out using the polymerase chain reaction coupled with restriction fragment length polymorphism. Using multivariate logistic regression analysis, we found that individuals with the AA genotype of IL10 rs1800896 showed an increased risk of liver cirrhosis compared with those with the GG genotype in a codominant model (OR = 2.01, 95%CI = 1.10-3.65). In dominant and recessive models, we found that the IL10 rs1800896 polymorphism was correlated with the development of liver cirrhosis (for the dominant model, OR = 1.46, 95%CI = 1.01-2.13; for the recessive model, OR = 1.72, 95%CI = 1.01-3.02). In summary, our study suggests that the IL10 rs1800896 polymorphism is associated with the development of liver cirrhosis.

Single-breath vital capacity high concentration sevoflurane induction in children: with or without nitrous oxide?

BACKGROUND: Single-breath vital capacity inhalation induction with high concentration sevoflurane (SBVC-HC) is a rapid and 'needleless' technique, preferred and well tolerated in the cooperative child. The addition of nitrous oxide may speed up induction by its second gas effects. Previous studies done in children looking at the effect of N(2)O on this technique lacked power and showed conflicting results. This study aims to investigate the effect of N(2)O on induction time for SBVC-HC sevoflurane induction in children. METHODS: Eighty unpremedicated, ASA I and II children, aged 5-15 yr having elective surgical procedures under general anaesthesia, were recruited and randomized to: Group A: 8% sevoflurane in O(2) 6 litre min(-1), and Group B: 8% sevoflurane in N(2)O 4 litre min(-1) and O(2) 2 litre min(-1). The primary outcome was the time to 'loss of eyelash reflex'. The time to return of 'regular respiration' and 'conjugate gaze' were also noted. RESULTS: The difference in the 'time to loss of eyelash reflex' was small but statistically significant. Group B: mean duration 53.6 s, standard deviation (SD) 16.1, compared with Group A: 63.5 s, SD 16.1 (mean difference 9.9, 95% confidence interval 2.5-17.3, P=0.01). Differences in the time to return of 'regular breathing' and 'conjugate gaze' were not statistically significant. Patients receiving N(2)O had less excitatory movements (P=0.007), but incidence of other adverse events was low and did not differ significantly between both groups. More than 94% of children would choose this method of induction again in both groups. CONCLUSIONS: We conclude that for SBVC-HC sevoflurane induction in children, the addition of N(2)O resulted in faster loss of consciousness and reduced excitatory movements.

Arecoline-stimulated placenta growth factor production in gingival epithelial cells: modulation by curcumin.

OBJECTIVE: Placenta growth factor (PlGF) is associated with the progression and prognosis of oral cancer. MATERIALS AND METHODS: This study used ELISA, quantitative polymerase chain reaction, and Western blotting to study the arecoline-stimulated (PlGF) protein or mRNA expression in human gingival epithelial S-G cells. RESULTS: Arecoline, a major areca nut alkaloid and an oral carcinogen, could stimulate PlGF protein synthesis in S-G cells in a dose- and time-dependent manner. The levels of PlGF protein secretion increased about 3.1- and 3.8-fold after 24-h exposure to 0.4 and 0.8 mM arecoline, respectively. Pretreatment with antioxidant N-acetyl-l-cysteine (NAC) and ERK inhibitor PD98059, but not NF-κB inhibitor Bay 11-7082, JNK inhibitor SP600125, p38 MAPK inhibitor SB203580, and PI3-K inhibitor LY294002, significantly reduced arecoline-induced PlGF protein synthesis. ELISA analyses demonstrated that NAC and PD98059 reduced about 43% and 38% of the arecoline-induced PlGF protein secretion, respectively. However, combined treatment with NAC and PD98059 did not show additive effect. Moreover, 10 µM curcumin and 4 mM NAC significantly inhibited arecoline-induced ERK activation. Furthermore, 10 µM curcumin completely blocked arecoline-induced PlGF mRNA expression. CONCLUSION: Arecoline-induced PlGF synthesis is probably mediated by reactive oxygen species/ERK pathways, and curcumin may be an useful agent in controlling oral carcinogenesis.

Minocycline-induced chemical pneumonitis and its successful treatment: a case report.

Chemical pleurodesis is an effective treatment for persistent air leakage and secondary pneumothorax. We report the case of a 57-year-old man who presented with pneumothorax and was treated by tube thoracostomy. Because of malpositioning of the chest tube, the minocycline that was administered for pleurodesis was injected into the lung parenchyma instead, which induced chemical pneumonitis. A review of literature indicated that this is the first report of minocycline-associated chemical pneumonitis and its successful treatment.

Systemic steroids in acute exacerbation of COPD - from guidelines to bedside.

The optimal steroid dosages in AECOPD are still under debate. Admission records of patients in our hospital from January to December 2008 due to a diagnosis of AECOPD were reviewed. More wheezing and tachypnea were noted in the patients with a maximal daily prednisolone dose more than 60 mg. The steroid dose was higher in AECOPD without pneumonia than those concurrent with pneumonia. Those who had concurrent pneumonia had a higher risk of nosocomial infections. The study reflects the heterogeneity of AECOPD and that steroid dosages were determined by the clinical evaluation of the severity of illness and bacterial infections.

Post-tooth extraction sepsis without locoregional infection--a population-based study in Taiwan.

OBJECTIVE: To investigate the incidence and risk factors of post-tooth extraction sepsis in patients without locoregional infection. SUBJECTS AND METHODS: We assessed all claim records of the Taiwanese National Health Insurance program in 2005. Admissions for patients aged > or =16 years containing a discharge diagnosis of sepsis, and who received tooth extraction within 14 days before the admission were identified. Patient charts were reviewed to confirm the diagnosis of sepsis and rule out other infection sources. The relationship between postextraction sepsis (PES) and clinical parameters was analyzed. RESULTS: Thirty-three of the 2 223 971 extraction cases met the criteria of PES, an incidence of 1.48 per 100 000, and seven patients (21.2%) died of the disease. Aging significantly increased the risk of PES (P < 0.001). Pre-existing comorbidities were found in 20 of the 33 cases, with diabetes mellitus and hematologic diseases the most common. The method, number, and position of extraction had no influence on PES incidence. Blood cultures were positive in 25 patients (75.8%) and isolates included species of the Streptococcus, Actinomyces, Klebsiella, Bacteroides, Prevotella, and Enterococcus genera. CONCLUSION: Tooth extraction is associated with a low but significant risk of postoperative sepsis, especially in the elderly and patients with underlying diseases.

Atomic replacement effects on the band structure of doped perovskite thin films.

The potential applications of perovskite manganite R1-xAxMnO3 (R = rare earth element; A = Sr, Ca) thin films have been continuously explored due to their multi-functional properties. In particular, the optimally hole-doped La0.67Ca0.33MnO3 thin film demonstrates a colossal magneto-resistance that is beneficial to the performance of spintronic devices. To understand the effect of R and A ions on the material properties, we systematically measure the resistivity, magnetization, and electronic energy states for three optimally hole-doped R0.67A0.33MnO3 thin films with R = La, Sm and A = Sr, Ca. Various energy parameters are derived based on the X-ray absorption and X-ray photoelectron spectra, including the band gap, the charge frustration energy and the magnetic exchange energy. It is interesting to find that the replacement of La with Sm is more effective than that of Sr with Ca in terms of tuning the electrical property, the Curie temperature, and the band gap. The strain-induced reduction of the O 2p- Mn 3d hybridization and the interplay of R/A site disorder and strain effect are discussed. The results of this study provide useful information for the band design of perovskite oxide films.

[A follow-up study on the clinical characteristics among patients with diabetes mellitus combined with acute myocardial infarction].

Objective: To investigate the clinical characteristics of diabetic patients combined with acute myocardial infarction (AMI) and to compare the prognosis between diabetic and non- diabetic patients in 4-5 years after the onset of AMI. Methods: Followed the certain inclusive and exclusive criteria, a total of 420 patients with acute myocardial infarction were included and divided into diabetes group (group D) and non-diabetes group (group N) with numbers as 161 people and 259 respectively. Baseline data, clinical information, short-term outcome and long-term prognosis of the two groups were compared and analyzed. Results: Among the patients with diabetes, the average age was older (65.65±11.33 vs. 63.30±15.34), with fewer males (64.59% vs. 79.92%); and more likely to have other complications as hypertension (64.60% vs. 53.28%) or hyperlipidemia (42.24% vs. 26.25%). 59.29% of the patients in group D showed pathological changes in 3 major coronary arteries, which were significantly more than its counterpart (40.83%). The proportion of patients that had undergone the coronary artery bypass, grafting (11.11% vs. 5.31%) appeared also higher. There was no significant difference seen in the short-term outcomes between the two groups, but results from the long-term follow-up program showed that both the incidence of Major Adverse Cardiovascular Events (MACE) (50.67% vs. 27.72%) and the all-cause mortality (20.00% vs. 9.90%) in group D were higher than those appeared in group N (27.72%). Conclusions: Patients suffered from the combination of both diabetes and acute myocardial infarction appeared older in age, more in females, with more complications and the coronary artery lesions were more severe and wider. During hospitalization, no significant difference was seen regarding the short-term outcomes between the two groups but the results from long-term follow-up process showing that the risk of MACE events was significantly higher in patients with type2 diabetes.

Strain effect on orbital and magnetic structures of Mn ions in epitaxial Nd0.35Sr0.65MnO3/SrTiO3 films using X-ray diffraction and absorption.

This study probes the temperature-dependent strain that is strongly correlated with the orbital and magnetic structures of epitaxial films of Nd0.35Sr0.65MnO3 (NSMO) that are fabricated by pulsed laser deposition with two thicknesses, 17 (NS17) and 103 nm (NS103) on SrTiO3 (STO) substrate. This investigation is probed using X-ray diffraction (XRD) and absorption-based techniques, X-ray linear dichroism (XLD) and the X-ray magnetic circular dichroism (XMCD). XRD indicates a significant shift in the (004) peak position that is associated with larger strain in NS17 relative to that of NS103 at both 30 and 300 K. Experimental and atomic multiplet simulated temperature-dependent Mn L3,2-edge XLD results reveal that the stronger strain in a thinner NS17 film causes less splitting of Mn 3d eg state at low temperature, indicating an enhancement of orbital fluctuations in the band above the Fermi level. This greater Mn 3d orbital fluctuation can be the cause of both the enhanced ferromagnetism (FM) as a result of spin moments and the reduced Néel temperature of C-type antiferromagnetism (AFM) in NS17, leading to the FM coupling of the canted-antiferromagnetism (FM-cAFM) state in NSMO/STO epitaxial films at low temperature (T = 30 K). These findings are also confirmed by Mn L3,2-edge XMCD measurements.

Increased expression of placenta growth factor in COPD.

BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptor may have an important role in the pathogenesis of emphysema. The effect of another angiogenic factor, placenta growth factor (PlGF), in chronic obstructive pulmonary disease (COPD) is unknown. METHODS: The serum levels of VEGF and PlGF in patients with COPD (n = 184), smokers (n = 212) and non-smokers (n = 159) and the bronchoalveolar lavage (BAL) fluid levels of VEGF and PlGF in another group (20 patients with COPD, 18 controls) were measured. In vitro cell culture experiments were performed to investigate the effect of PlGF on VEGF. RESULTS: The mean (SE) serum levels of PlGF were significantly higher in patients with COPD than in controls (27.1 (7.4) pg/ml vs 12.3 (5.1) pg/ml in smokers and 10.8 (6.3) pg/ml in non-smokers, p = 0.005). The levels of PlGF in BAL fluid were also significantly higher in patients with COPD than in controls (45.7 (12.3) pg/ml vs 23.9 (7.6) pg/ml, p = 0.005), associated with an increase in the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8). In patients with COPD the levels of PlGF correlated inversely with forced expiratory volume in 1 s (FEV(1)) in serum (r = -0.59, p = 0.002) and in BAL fluid (r = -0.51, p = 0.001). While the serum levels of VEGF were the same in patients with COPD and controls, the BAL fluid levels were significantly lower in patients with COPD than in controls (127.5 (30.1) pg/ml vs 237.8 (36.1) pg/ml, p = 0.002). In cultured bronchial epithelial cells, proinflammatory cytokines induced an increase in the protein expression of both PlGF and VEGF. Continuous concomitant treatment with PlGF, TNF-alpha and IL-8 stimulation reduced VEGF expression and induced cell death. This phenomenon was suppressed by VEGF receptor inhibitor (CBO-P11). CONCLUSIONS: The serum and BAL fluid levels of PlGF are increased in patients with COPD and are inversely correlated with FEV(1). Concomitant treatment with PlGF, TNF-alpha and IL-8 causes detrimental effects on airway epithelial cells. These data suggest that bronchial epithelial cells can express PlGF, which may contribute to the pathogenesis of COPD.

Large-area Co-silicide nanodot arrays produced by colloidal nanosphere lithography and thermal annealing.

We report here the successful fabrication of large-area size-tunable periodic arrays of cobalt and Co-silicide nanodots on silicon substrates by employing the colloidal nanosphere lithography (NSL) technique and heat treatments. The growth of low-resistivity epitaxial CoSi(2) was found to be more favorable for the samples with smaller Co nanodot sizes. The sizes of the epitaxial CoSi(2) nanodots can be tuned from 50 to 100 nm by varying the diameter of the colloidal spheres and annealing temperatures. The epitaxial CoSi(2) nanodots were found to grow with an epitaxial orientation with respect to the (001)Si substrates: [001]CoSi(2)//[001]Si and (200)CoSi(2)//(400)Si. From the results of planview HRTEM, XTEM, and SAED analysis, the epitaxial CoSi(2) nanodots were identified to be inverse pyramids in shape, and the average sizes of the faceted silicide nanodots were measured to decrease with annealing temperature. The observed results present the exciting prospect that with appropriate controls, the colloidal NSL technique promises to facilitate the growth of a variety of well-ordered silicide nanodots with selected shape, size, and periodicity.

[Effects of casein phosphopeptide-amorphic calcium phosphate on enamel erosion: an in situ study].

Objective: To evaluate the effects of casein phosphopeptide-amorphic calcium phosphate (CPP-ACP) on enamel erosion using an improved in situ experimental protocol. Methods: Forty-eight enamel blocks were prepared from fresh-extracted human premolars and further embedded in the acrylic resins. The present study was divided into 2 parts. In part 1 of the study, two volunteers were recruited to test the availability and safety of the in situ erosion protocol. Customized intraoral appliance was made with 4 reservoirs containing the specimens for each volunteer. For each intraoral applicance, 2 reservoirs were made with the openings and the other 2 remained intact. All volunteers were instructed to drink 150 ml cola within 5 min using the gargling method after placing appliances intraorally for 2 h. After erosion, the appliances were remained undisturbed intraorally for 1 h until the next erosive attack. The in situ erosion cycles were performed 4 times daily over 7 d. In part 2 of the study, forty specimens were randomly divided into 2 groups (n=20): CPP-ACP group and control group. The surfaces of specimens in CPP-ACP group were pretreated with CPP-ACP for 3 min before in situ erosion, whereas the specimens in control group were pretreated with deionized water for 3 min. For each intraoral applicance, 4 reservoirs were made with openings. Ten healthy volunteers were recruited and the above-mentioned in situ erosion protocol was applied to test the effects of CPP-ACP on enamel erosion. The surface microhardness and surface microstructure of the samples were examined before and after erosion in both parts of the study. The data were statistically analyzed using ANOVA and LSD tests. Data were considered statistically significant at a level of P<0.05. Results: Significant surface softening was observed in all specimens after erosion (P<0.001). The surface microhardness in the CPP-ACP group and control group were (198.8±23.2) and (152.4±42.1) HV, respectively (P=0.040). The specimens in the CPP-ACP group showed significantly fewer changes in surface microstructure compared with those in the control group. Conclusions: Based on this in situ experimental protocol, short-time consuming of acid beverages would produce significant effects on the surface microhardness of the human enamel, whereas the application of CPP-ACP can increase the erosion resistance of the enamel.

Paradoxical response during anti-tuberculosis treatment in HIV-negative patients with pulmonary tuberculosis.

BACKGROUND: Transient worsening of tuberculosis (TB) symptoms and lesions following anti-tuberculosis treatment (paradoxical response [PR]), has been described in human immunodeficiency virus (HIV) infected patients who undergo anti-tuberculosis treatment. The frequency and clinical presentations for PR in HIV-negative patients with pulmonary TB are unknown. OBJECTIVE: To determine the incidence of PR and its associated manifestations in a retrospective study of HIV-negative patients with pulmonary TB. RESULTS: Of 659 TB patients, 16 developed PR, with an incidence of 2.4%. The medium onset time of PR was 26 days. Recurrent fever was the most common clinical manifestation. Compared with 643 patients without PR, patients developing PR had significantly decreased haemoglobin, albumin, body mass index and baseline lymphocyte counts. There was a noticeable increase in the lymphocyte count during paradoxical deterioration in PR subjects than in the control group. Independent factors for developing PR included anaemia, hypoalbuminaemia, lymphopaenia and lymphocyte count increase during PR development. CONCLUSIONS: The clinical manifestations of PR in patients with pulmonary TB were different from those in patients with extra-pulmonary TB. Baseline anaemia, hypoalbuminaemia, lymphopaenia and a greater change in lymphocyte count were independent risk factors for developing PR.

A T-cell-selective interleukin 2 mutein exhibits potent antitumor activity and is well tolerated in vivo.

Human interleukin 2 (IL-2; Proleukin) is an approved therapeutic for advanced-stage metastatic cancer; however, its use is restricted because of severe systemic toxicity. Its function as a central mediator of T-cell activation may contribute to its efficacy for cancer therapy. However, activation of natural killer (NK) cells by therapeutically administered IL-2 may mediate toxicity. Here we have used targeted mutagenesis of human IL-2 to generate a mutein with approximately 3,000-fold in vitro selectivity for T cells over NK cells relative to wild-type IL-2. We compared the variant, termed BAY 50-4798, with human IL-2 (Proleukin) in a therapeutic dosing regimen in chimpanzees, and found that although the T-cell mobilization and activation properties of BAY 50-4798 were comparable to human IL-2, BAY 50-4798 was better tolerated in the chimpanzee. BAY 50-4798 was also shown to inhibit metastasis in a mouse tumor model. These results indicate that BAY 50-4798 may exhibit a greater therapeutic index than IL-2 in humans in the treatment of cancer and AIDS.

Gap junctional communication modulates gene expression in osteoblastic cells.

Bone-forming cells are organized in a multicellular network interconnected by gap junctions. In these cells, gap junctions are formed by connexin43 (Cx43) and connexin45 (Cx45). Cx43 gap junctions form pores that are more permeable to negatively charged dyes such as Lucifer yellow and calcein than are Cx45 pores. We studied whether altering gap junctional communication by manipulating the relative expression of Cx43 and Cx45 affects the osteoblast phenotype. Transfection of Cx45 in cells that express primarily Cx43 (ROS 17/2.8 and MC3T3-E1) decreased both dye transfer and expression of osteocalcin (OC) and bone sialoprotein (BSP), genes pivotal to bone matrix formation and calcification. Conversely, transfection of Cx43 into cells that express predominantly Cx45 (UMR 106-01) increased both cell coupling and expression of OC and BSP. Transient cotransfection of promoter-luciferase constructs and connexin expression vectors demonstrated that OC and BSP gene transcription was down-regulated by Cx45 cotransfection in ROS 17/2. 8 and MC3T3-E1 cells, in association with a decrease in dye coupling. Conversely, cotransfection of Cx43 in UMR 106-01 cells up-regulated OC and BSP gene transcription. Activity of other less specific osteoblast promoters, such as osteopontin and osteonectin, was less sensitive to changes in gap junctional communication. Thus, altering gap junctional permeability by manipulating the expression of Cx43 and Cx45 in osteoblastic cells alters transcriptional activity of osteoblast-specific promoters, presumably via modulation of signals that can diffuse from cell to cell. A communicating intercellular network is required for the full elaboration of a differentiated osteoblastic phenotype.

Insulin activates caspase-3 by a phosphatidylinositol 3'-kinase-dependent pathway.

Activation of the caspase proteases by c-Jun N-terminal kinase 1 (JNK1) has been proposed as a mechanism of apoptotic cell death. Here we report that insulin activates caspase-3 by a pathway requiring phosphatidylinositol 3'-kinase (PI3-kinase). JNK1 assays demonstrated that insulin treatment of myeloma cells induced 3-fold activation of JNK1. Inhibition of PI3-kinase with wortmannin and LY294002 blocked insulin-dependent activation of JNK1. Caspase assays demonstrated that insulin increased caspase-3 activity 3-fold and that inhibition of PI3-kinase blocked this effect. Cell death was doubled by insulin and was due to a 3-fold increase in apoptosis of cells in the G1/G0 phase of the cell cycle. Inhibition of PI3-kinase completely blocked this effect. Finally, inhibition of caspase-3 with benzyloxycarbonyl-Asp-2,6-dichlorobenzoyloxymethylketone blocked cell death due to insulin. Taken together, these findings indicate that insulin activates caspase-3 by a PI3-kinase-dependent pathway resulting in increased apoptosis and cell death.

A dominant negative cadherin inhibits osteoblast differentiation.

We have previously indicated that human osteoblasts express a repertoire of cadherins and that perturbation of cadherin-mediated cell-cell interaction reduces bone morphogenetic protein 2 (BMP-2) stimulation of alkaline phosphatase activity. To test whether inhibition of cadherin function interferes with osteoblast function, we expressed a truncated N-cadherin mutant (NCaddeltaC) with dominant negative action in MC3T3-E1 osteoblastic cells. In stably transfected clones, calcium-dependent cell-cell adhesion was decreased by 50%. Analysis of matrix protein expression during a 4-week culture period revealed that bone sialoprotein, osteocalcin, and type I collagen were substantially inhibited with time in culture, whereas osteopontin transiently increased. Basal alkaline phosphatase activity declined in cells expressing NCaddeltaC, relative to control cells, after 3 weeks in culture, and their cell proliferation rate was reduced moderately (17%). Finally, 45Ca uptake, an index of matrix mineralization, was decreased by 35% in NCaddeltaC-expressing cells compared with control cultures after 4 weeks in medium containing ascorbic acid and beta-glycerophosphate. Similarly, BMP-2 stimulation of alkaline phosphatase activity and bone sialoprotein and osteopontin expression also were curtailed in NCaddeltaC cells. Therefore, expression of dominant negative cadherin results in decreased cell-cell adhesion associated with altered bone matrix protein expression and decreased matrix mineralization. Cadherin-mediated cell-cell adhesion is involved in regulating the function of bone-forming cells.

Characterization and hormonal modulation of IL-1 binding in neonatal mouse osteoblastlike cells.

Considerable evidence indicates that interleukin-1 (IL-1) is a potent regulator of bone cell activity. Consequently, we studied its binding to neonatal mouse osteoblastlike cells. Purified, labeled recombinant IL-1 alpha bound specifically to neonatal mouse osteoblastlike cells with a dissociation constant of 30-200 pM at 22 degrees C. There were 3000-15,000 receptors per cell. IL-1 bound to cell surfaces at 4 degrees C was rapidly internalized when the temperature was raised to 37 degrees C. Receptor specificity was confirmed by demonstrating that, among a series of 11 polypeptides, only IL-1 inhibited 125I-IL-1 binding. Treatment of surface-bound 125I-IL-1 alpha with a bivalent water-soluble cross-linker identified a membrane peptide of Mr 70,000 cross-linked to IL-1. The apparent IL-1 receptor was solubilized from a plasma membrane-enriched fraction using 3-[(3-cholamidopropyldimethylammonio]-1-propanesulfonate (CHAP). The resulting material exhibited specific IL-1 binding. Preincubation of cells with IL-1, retinoic acid, transforming growth factor beta (TGF-beta), or phorbol ester caused a reduction in apparent receptor numbers per cell, while preincubation with epidermal growth factor (EGF), dexamethasone, or parathyroid hormone (PTH) increased receptor numbers per cell. Preincubation with insulin, vitamin D, prostaglandin E2 (PGE2), interferon-gamma (IFN-gamma), and 17 beta-estradiol had no effect. These results suggest that specific, high-affinity IL-1 receptors are present on osteoblastlike cells and that the receptor number can be modified by various osteotropic agents. Regulation of bone cell IL-1 receptors may contribute to the control of bone remodeling.