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Biomedical subjects

A Salmi

Publications and source records attributed to A Salmi.

At least 19 recordsLinked to original sources

The effect of intrauterine levonorgestrel use on the expression of c-JUN, oestrogen receptors, progesterone receptors and Ki-67 in human endometrium.

The major regulators of endometrial function are oestrogen and progesterone, which act through binding their nuclear receptors and by activating transcription of their target genes. Interactions between steroid receptors and transcription proteins, e.g. c-JUN/AP-1, can modulate steroid action at the transcriptional level. The 19-nortestosterone-derived progestin, levonorgestrel, is used for contraception, treatment of menorrhagia and for endometrial protection during hormone replacement therapy, but the signalling pathways of its action are totally undefined. We examined the effect of an intrauterine system, releasing 20 microg of levonorgestrel per 24 h (LNG-IUS), on immunoreactive oestrogen receptor, progesterone receptor, c-JUN and Ki-67 expression in 29 endometrial specimens, obtained from fertile women using the LNG-IUS for contraception. Moderate to strong immunostaining for oestrogen receptors was observed in the stromal cells in all specimens, in glandular epithelial cells in 26 cases and in flattened luminal epithelial cells in 17 specimens. Decidualized stromal cells showed no progesterone receptor immunoreactivity in 19 of the 29 specimens, and weak to moderate immunostaining in 10 cases. Luminal epithelial cells were negative for progesterone receptor in all samples. Intense nuclear staining for C-JUN was observed in epithelial cells in 26 and in decidualized stromal cells in all 29 of the samples. In 16 samples, Ki-67 immunoreactivity was evaluated as weak to moderate in decidualized stroma, and in 13 samples absent. Our data demonstrate that intrauterine release of LNG maintains constant expression of C-JUN and exerts progestational effects in the endometrium in the absence of progesterone receptors. In contrast, LNG-IUS inhibits several cellular responses to oestrogen despite the presence of endogenous oestrogen and oestrogen receptors. These data suggest that the progestational effects induced by progesterone and levonorgestrel are mediated through different signalling pathways.

Adult

Ultrasound-guided fine needle biopsy of pancreatic masses: results of a multicenter study.

OBJECTIVE: The aim of this study was to investigate the results of ultrasound-guided fine needle biopsy of pancreatic masses in a large multicenter series. METHODS: This study collected the data of 510 patients who had a final diagnosis available and who had undergone ultrasound-guided fine needle biopsy of the pancreas. Retrieval rate, sensitivity, specificity, and overall diagnostic accuracy of the whole series, by three different bioptic procedures (cytology, histology, and cytology plus histology) were evaluated. The reliability of ultrasound-guided fine needle biopsy to allow a correct diagnosis in the different pancreatic pathologies was calculated. Finally, any complications were collected. RESULTS: For cytology, histology, and cytology plus histology, retrieval rate values were: 94%, 96%, and 97%; sensitivity was: 87%, 94%, and 94%, specificity: 100%; and diagnostic accuracy: 91%, 90%, and 95%, respectively. Ultrasound-guided fine-needle biopsy correctly diagnosed all the cases of pancreatic metastases or non-Hodgkin's lymphoma (23 of 510 cases as 5%; in eight of 23 it led to the first diagnosis of the primary tumor) and all the cases of abscesses, 97% of the cases of pseudocysts, 86% of pancreatic adenocarcinomas, 62% of cystic neoplasms, 35% of the cases of chronic pancreatitis (in this case, the bioptic procedures were reviewed), and 33% of neuroendocrine tumors. There were complications in one case of asymptomatic peripancreatic hematoma, three cases of vaso-vagal reactions, and 21 cases of pain. CONCLUSION: Ultrasound-guided fine needle biopsy of the pancreas is efficacious, without any difference between the various bioptic modalities (with the exception of chronic pancreatitis, in which histology is better). The technique is safe. Moreover, the procedure allows the identification of patients affected by pancreatic tumors other than adenocarcinoma (in our survey 5% of the total); in about one third of these patients it leads to the diagnosis of the primary tumor, thus avoiding inappropriate treatments.

Biopsy, Needle

Cellular localization of c-jun messenger ribonucleic acid and protein and their relation to the proliferation marker Ki-67 in the human endometrium.

We studied cellular c-jun messenger RNA (mRNA) expression in the human endometrium during the menstrual cycle (n = 47) and in human decidua during pregnancy (n = 8), by using digoxigenin-labeled RNA probes in in situ hybridization. The same tissue samples were also analyzed for c-Jun protein and the proliferation marker Ki-67. In the proliferative endometrium, strong expression of c-jun was detected in luminal and glandular epithelium as well as in fibroblast-like stromal cells. During the early luteal phase, strong hybridization signals were identified in both epithelial and stromal compartments, with the strongest hybridization in the stromal cells beneath the epithelium. c-jun mRNA was markedly diminished in luminal and glandular epithelia of mid- and late secretory phase endometria, but it remained unchanged in the stroma. Regardless of the phase of the menstrual cycle, significant hybridization was identified in endothelial cells in the endometrium and myometrium, and a low signal was detected in myometrial muscle cells as well. During early gestation, weak expression of c-jun mRNA was observed in glandular epithelial cells and in decidualized stromal cells. In term pregnancy decidua, only low-level hybridization was detected in a few decidual cells. Nuclear immunostaining of c-Jun was detected in luminal and glandular epithelia and in stroma throughout the menstrual cycle. The location of Ki-67 antigen was temporally related to the c-jun mRNA expression in cycling endometrium and pregnancy decidua. From our data we conclude that 1) c-jun mRNA is differentially expressed in endometrial epithelial and stromal cells; 2) c-jun mRNA is cyclically regulated in the human endometrial epithelium; 3) c-jun mRNA expression is temporally related to epithelial proliferation in the endometrium; and 4) c-Jun protein is present in the human endometrium throughout the menstrual cycle.

Cell Nucleus

Ultrasonography-detected macroregenerative nodules in cirrhosis: a prospective study.

BACKGROUND & AIMS: The preneoplastic role of macroregenerative nodules in cirrhosis is still debated. Thirty-two consecutive ultrasonography-detected macronodules were followed up to evaluate whether and which lesions are the actual precursors of hepatocellular carcinoma, if histology can identify preneoplastic macronodules, and whether additional parameters are related to neoplastic evolution. METHODS: Macroregenerative nodule classification was based on recently proposed histological criteria. Extranodular liver cell dysplasia was also evaluated. The follow-up included ultrasonography and serum alpha-fetoprotein level determination every 3 months. RESULTS: Twenty-two macronodules (78%) were classified as typical and 7 (22%) as atypical. Twenty-one were hypoechoic, and 11 were hyperechoic. Extranodular dysplasia was more frequently associated with atypical than typical macronodules (5 of 7 vs. 6 of 22). After 28 +/- 15 months, neoplastic transformation occurred in 8 macronodules (25%) and was more frequent in atypical than in typical (5 of 7 vs. 3 of 25), in hyperechoic than in hypoechoic (5 of 11 vs. 3 of 21), and in extranodular dysplasia-associated macronodules than in extranodular dysplasia-free macronodules (5 of 11 vs. 2 of 18). Five hepatocellular carcinomas appeared outside the original macronodule. CONCLUSIONS: Atypical macroregenerative nodules can be considered precursors of hepatocellular carcinoma. Histology is useful in identifying preneoplastic macronodules, and hyperechoic pattern and extranodular dysplasia are additional risk factors for neoplastic transformation.

Aged

The interleukin-1 system in gestational tissues at term: effect of labour.

Previous studies suggest that the interleukin-1 (IL-1) system is involved in preterm labour, at least in cases associated with intrauterine infection. To investigate the effect of term labour without infection on the IL-1 system, the messenger ribonucleic acid (mRNA) expression of IL-1 beta, IL-1 receptor type I (IL-1R tI), IL-1 receptor antagonist (IL-1ra), and IL-1 beta converting enzyme (ICE) were examined by Northern blot analysis and by reverse transcriptase-polymerase chain reaction (RT-PCR) in paired samples of decidua and placenta obtained from women having spontaneous vaginal delivery (group 1) or elective caesarean section (group 2) at term. In addition, concentrations of IL-1 beta and IL-1ra proteins were measured by ELISA in paired decidual and placental cytosols. In all decidual samples, IL-1 beta mRNA was expressed strongly, and the IL-1 beta concentration was 40- to 50-fold higher than in paired placental samples, in which the signal for IL-1 beta mRNA could be detected by RT-PCR only, and the amount of IL-1 beta protein was undetectable or very low. A comparison between the study groups revealed that the decidual IL-1 beta mRNA level tended to be higher in group 1, and the median IL-1 beta concentration in decidual cytosols was significantly higher in group 1 than in group 2 (P < 0.05). The IL-1R tI mRNA transcript was stronger in decidual than in paired placental samples in both groups. The mRNAs encoding ICE and IL-1ra were detected by RT-PCR in decidual and placental samples from both groups. The IL-1ra concentration tended to be higher in decidual cytosols than in paired placental cytosols, but there was no difference between the study groups. The IL-1ra/IL-1 beta ratio was significantly lower in decidual samples in women with spontaneous labour than in women without labour (P < 0.05). The results of this study confirm that decidua is the major site of IL-1 beta production and action in term gestational tissues. Furthermore, the results show that the major change in decidual/placental IL-1 system during parturition is the increase in decidual IL-1 beta production. Whether the increased IL-1 beta production precedes or is a consequence of labour, remains still unclear.

Adult

Therapy with antibody against leukocyte integrin VLA-4 (CD49d) is effective and safe in virus-facilitated experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is facilitated in resistant BALB/c mice by intraperitoneal infection with an avirulent Semliki Forest virus (SFV-A7). Viral infection increases the incidence of EAE from 15-30% to 60-90% and speeds up appearance of paralysis from 24 to 14 days. In this paper, we describe treatment of virus-facilitated EAE with monoclonal antibodies (mAbs) against leukocyte and/or endothelial cell adhesion molecules. Therapy with mAb against ICAM-1 (intercellular adhesion molecule-1) had a modest effect, but caused hemorrhagic brain and spinal cord lesions. Therapy with mAb against Mac-1 (alpha M beta 2-integrin) was well tolerated but had no effect. Therapy with mAb against VLA-4 (alpha 4 beta 1-integrin) was safe, diminished both clinical and histopathological signs of EAE, decreased induction of VCAM-1 (vascular cell adhesion molecule-1) on brain vessels and diminished infiltration of VLA-4+ cells into the brain. The amount of viral antigen in the brain was not altered. We conclude that facilitation of leukocyte entry into the brain is a major mechanism for viral facilitation of EAE in the BALB/c mouse, and that facilitation can be inhibited by anti-adhesion therapy. This may have implications for treatment of relapses triggered by viral infections in multiple sclerosis.

Animals

mRNA expression of insulin-like growth factor-I (IGF-I) is suppressed and those of IGF-II and IGF-binding protein-1 are constantly expressed in the endometrium during use of an intrauterine levonorgestrel system.

Insulin-like growth factors (IGF-I and IGF-II) are believed to mediate and modulate steroid hormone actions in the endometrium. In this study we determined the effects of an intrauterine system (IUS), releasing 20 microg levonorgestrel (LNG) daily, on endometrial expression of mRNAs encoding IGFs and insulin-like growth factor binding protein (IGFBP)-1. In Northern blotting, IGF-I mRNA was undetectable in all endometrial specimens from women with an LNG-IUS (n = 11) and in pregnancy decidua, whereas several transcripts of 0.6-7.6 kb were detected in proliferative and secretory phase endometria. In contrast, mRNAs encoding IGF-II and IGFBP-1 were strongly expressed in pregnancy and in all endometrial samples from women with an LNG-IUS, but were undetectable in proliferative or early to mid-secretory phase endometria. Using the more sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) method, IGF-I and IGF-II mRNAs were detectable in all cycling endometria, in early pregnancy decidua and in LNG-exposed endometrium. IGFBP-1 mRNA was constantly expressed in LNG-exposed endometrium, in early pregnancy decidua and in premenstrual endometrium, but was undetectable in all specimens from proliferative or early to mid-secretory endometrium. Our data demonstrate that progestin treatment can affect the gene expression of endometrial growth factors in vivo. The consistent expression of mRNAs encoding IGF-II and IGFBP-1, with suppression of IGF-I mRNA in endometria exposed to LNG, suggests that this mode of hormone treatment can inhibit IGF-I action in the endometrium. If IGF-I mediates and modulates oestrogen action, suppression of IGF-I mRNA may be one of the molecular mechanisms which accounts for the antiproliferative effects of progestogens on oestrogen-primed endometrium and the atrophy of endometrial epithelium resulting from use of an LNG-IUS.

Adult

Percutaneous ethanol injection in the treatment of hepatocellular carcinoma. A multicenter survey of evaluation practices and complication rates.

BACKGROUND: Percutaneous ethanol injection (PEI) has become a widely used procedure in the treatment of hepatocellular carcinoma (HCC). However, the criteria for selecting patients are not standardized, and little information is available about the complications of the procedure. METHODS: A questionnaire was sent to 11 experienced Italian centers. It investigated: the size and the number of HCC nodules suitable for treatment and the Child-Pugh risk class of the associated cirrhosis; the performance of the procedure; the number and characteristics of the patients treated; and, finally, any complications. RESULTS: Most of the centers performed PEI in single HCC nodules less than 5 cm in diameter or in multiple nodules if fewer than three, the larger being less than 3 cm. Patients in Child-Pugh's classes A, B, and C with single nodules were generally considered for PEI. A prothrombin time of less than 40% and a platelet count of less than 40,000/mm3 contraindicated PEI in most of the centers. PEI was generally performed on outpatients, using Chiba or spinal needles. One thousand and sixty-six patients (8118 sessions) were enrolled; 74% had a single HCC nodule and 26% multiple nodules. All except four had cirrhosis; 53% were in Child class A, 38% in class B, and 9% in class C. The mean number of sessions needed to destroy an HCC nodule was 6.7 (range, 2-14), with a mean alcohol injection volume of 5.0 ml per session (range, 2-20 ml). One death (0.09%) and 34 complications (3.2%) were reported. Among the complications we call attention to the hemorrhagic ones (eight cases) and tumoral seeding (seven cases). Severe pain experienced during the maneuver led to discontinuation of the procedure in 3.7% of the patients; 13.5% of the patients required analgesics and 24% had fever after PEI. CONCLUSIONS: Some procedural aspects of PEI treatment differ among the various centers a standardization is advisable. In the present survey PEI is a low-risk technique.

Aged

C-fos and c-jun expression in human endometrium and myometrium.

Estrogen is a mitogen in human endometrium and is considered to be responsible also for myometrial cell proliferation. Signalling pathways of estrogen action in these tissues are not known. In various other estrogen responsive cells, estrogen induces transient expressions of c-fos and c-jun mRNAs. We examined c-fos and c-jun mRNA expressions by Northern blotting in paired samples of endometrium, myometrium and leiomyoma tissues obtained from women under various hormonal environments as well as of endometrium and myometrium at term pregnancy. In nonpregnant endometria, strong expressions of c-fos (2.2 kb) and of c-jun (2.7 kb and 3.2 kb) were detected both in the follicular and luteal phase of the menstrual cycle, and the c-fos expression was significantly stronger in proliferative phase endometrium than in the adjacent myometrium. In most of the myometrial and leiomyoma tissue samples the signals for both protooncogenes were weak, and there were no systematic differences in the expressions between normal myometrium and myomatous tissue. In pregnant endometrium and myometrium, both the c-fos and c-jun mRNA expressions were nearly undetectable, and in pregnant endometrium expressions were significantly lower than those in nonpregnant endometrium. Also in late pregnancy myometria, the expression of c-jun was significantly lower than in nonpregnant tissues. These data suggest that c-fos and c-jun activation may be a part of estrogen-induced signal transduction in the endometrium, and that in term pregnancy endometrium this signalling pathway is inhibited. Due to the strong expression of c-jun and c-fos both in the proliferative and secretory phase endometrium, it is likely that these protooncogenes are related to functions other than epithelial cell proliferation in human endometrium. The weak expressions of c-fos and c-jun in the myometrium and in leiomyomata suggest that signalling pathways mediating steroid hormone action in endometrium and myometrium are different.

Adult

Natural history of focal nodular hyperplasia of the liver: an ultrasound study.

Sixteen cases of focal nodular hyperplasia (FNH) of the liver were followed by ultrasound (US) for a mean of 33 months (range 6-81). In 69% of the cases, the diagnosis was incidental. On US the lesions were single in 75% of the cases, localized in the right lobe in 75%, and subcapsular in 50%. No specific US-pattern could be identified. A central scar was found in 19% of the patients. At the end of the follow-up, the size was reduced in 7/16 cases, and in 1/16 the lesion disappeared. The spontaneous reduction of nodules in FNH must be considered in the management of this pseudotumor.

Adult

Measles virus hemagglutinin mediates monocyte aggregation and increased adherence to measles-infected endothelial cells.

The effect of measles virus (MV) infection on monocyte adhesion was studied using human peripheral blood monocytes and monocytic and endothelial cell lines. The infection of monocytic U-937 cells led to the formation of large cellular aggregates. Aggregation was independent of intercellular adhesion molecule-1 (ICAM-1)/lymphocyte function-associated antigen-1 (LFA-1), but could be inhibited by monoclonal antibodies (mAb) against the MV hemagglutinin glycoprotein (MV-H). mAb against the MV receptor, CD46, also blocked aggregation. No significant changes in the cell surface expression of adhesion molecules CD11a, CD11b, CD11c, CD18, CD54, CD44, CD49d (alpha 4-integrin) and CD62L (L-selectin) were observed on MV-infected monocytes. Infection of a human endothelial cell line, EAhy 926 (HEC), with MV led to a two-fold increase in 1CAM-1 expression and a two-fold increase in monocyte adherence to the HEC (from 22 +/- 1.6% to 42 +/- 4.8%). However, ICAM-1 mAb reduced monocyte adhesion to the control and MV-infected HEC to a similar degree, whereas anti-MV-H antibodies abolished the difference between binding to infected and control HEC. We conclude that MV hemagglutinin mediated both the homo typic aggregation in infected monocyte cultures and increased monocyte adherence to the infected endothelial cells.

Antibodies

Definition of three minimal T helper cell epitopes of rubella virus E1 glycoprotein.

To characterize T cell-recognized epitopes on rubella virus (RV) E1 glycoprotein, IL-2-dependent RV-specific T cell lines were established from 14 rubella-seropositive healthy donors. The responses of these lines were studied by using a panel of 94 partially overlapping synthetic peptides of 15 amino acids (aa) length covering the known nucleotide sequence of RVE1 glycoprotein. Two to seven peptide-defined epitopes were recognized by the T cell lines, but a large interindividual variation was found. T cell reactivity was most often localized to the regions between aa 276 and 290, aa 381 and 395 and aa 410 and 420. Analysis of overlapping, truncated peptides revealed three minimal T helper cell epitopes VIGSQARK, KFVTAALLN and RVIDPAAQ in aa positions 280-287, 385-393 and 412-419, respectively.

Animals

Proto-oncogenes c-jun and c-fos are down-regulated in human endometrium during pregnancy: relationship to oestrogen receptor status.

Oestrogen is the major stimulatory factor in endometrial cell proliferation. Animal and in-vitro studies have shown that proto-oncogenes c-fos and c-jun are regulated by oestrogen receptor (ER) complex. We have previously shown by Northern blot analysis that proto-oncogenes c-fos and c-jun are strongly expressed in human proliferative and early to mid-secretory endometrium. In this study, we examined the expression of the messenger RNA (mRNA) of the nuclear proto-oncogenes c-fos and c-jun in 10 early (6-10 weeks) and 20 term (30-40 weeks) pregnancy decidua by Northern blotting. In order to investigate the relationship between ER and these proto-oncogenes, the ER and progesterone receptors (PR) were identified in the same tissue samples by immunohistochemistry. When using 30-mer oligonucleotide probes, hardly any signals for c-fos and c-jun could be identified either in early or in late pregnancy decidua. Nuclear ER staining was intense in the epithelium and stroma of proliferative and early to mid-secretory endometrium but was sparsely scattered in stroma and lacking in epithelium during early pregnancy. In late pregnancy decidua, no positive ER staining was detectable. PR were present in abundance both in endometrial epithelium and stroma in proliferative and early secretory phase, and clear positive staining remained in stromal cells in late secretory phase and throughout pregnancy. The temporal association between immunoreactive ERs and the expression of c-fos and c-jun mRNA suggests that the activation of both proto-oncogenes is ER-mediated in human endometrium. The down-regulation of ER is one possible explanation for the repression of these immediate early genes during pregnancy.

Animals

A prospective study of changes in muscle dimensions following free-muscle transfer measured by ultrasound and CT scanning.

A retrospective study demonstrated that noninnervated free-muscle flaps do not lose bulk when evaluated at a mean of 41 months. The purpose of the present study was to evaluate changes in muscle bulk in noninnervated free-muscle transfers prospectively. This study included 22 flaps (17 latissimus dorsi, 4 rectus abdominis, and 1 gracilis). The thickness of the muscle was measured by ultrasonography preoperatively and 2 and 6 weeks and 3, 6, 9, 12, 15, 18, and 23 months postoperatively. The volume of the muscle was measured by computed tomographic (CT) scan preoperatively and 2 and 6 weeks and 3, 6, and 9 months postoperatively. Postoperative data were normalized to the preoperation measurements. The results demonstrated that the thickness of the muscle increased by a mean of 2.4 times (range 0.9 to 3.9) compared with the initial thickness in a 2-week period (p < 0.05), 2.0 times (range 0.9 to 4.2) in 6 weeks (p < 0.05), 1.7 times (range 0.8 to 4.2) in 3 months (p < 0.05), 1.5 times (range 0.6 to 3) in 6 months (p < 0.05), and 1.2 times (range 0.4 to 2.8) in 9 months (not significant). Thereafter, the mean thickness was the same as the initial thickness. CT scan measurements of the muscles confirmed the ultrasound findings. Our prospective study of free-muscle flaps found significant swelling that peaks at 2 weeks and extends until 6 months after the operation. This study also demonstrated that ultrasound evaluation of thickness gives the same conclusion as volumetric measurement by CT scanning.

Adolescent

Detection of rubella virus-specific immunoglobulin M antibodies with a baculovirus-expressed E1 protein.

The structural proteins of rubella virus (RV) were expressed in insect cells by using the baculovirus expression vector system. The recombinant E1 envelope glycoprotein was purified by immunoaffinity chromatography and used to detect RV-specific immunoglobulin M antibodies in a time-resolved fluoroimmunoassay. Correlation analysis between the reactivities of antibodies against this recombinant E1 and the reactivities against authentic RV antigen shows that purified E1 can detect RV antibodies of the immunoglobulin M type.

Antibodies, Viral

Use of ultrasonography to evaluate muscle thickness and blood flow in free flaps.

The purpose of this study was to investigate the common belief that a microvascular transfer of a non-innervated free muscle flap loses muscle bulk over time. Sixteen patients (latissimus dorsi = 8, rectus abdominis = 7, and gracilis muscle = 1) were evaluated an average of 41 months after free flap transfer. Latissimus dorsi and lower extremity flaps displayed significantly more swelling than the other flaps. Flap bulk was measured by ultrasound. The mean thickness of upper extremity flaps was 10.3 +/- 1.8 mm (control muscles 11.8 +/- 2.8), lower-extremity 14.5 +/- 3.7 mm (control muscles 10.9 +/- 0.7), latissimus dorsi 14.3 +/- 2.2 mm (control muscles 10.3 +/- 0.8, P = 0.018), and rectus abdominis 11.2 +/- 1.2 mm (control muscles 12.4 +/- 1.9). Color Doppler ultrasonography was used to detect the pedicles of the free flaps and also to measure the peak velocity of blood flow intramuscularly and in the pedicles. In the upper extremities (n = 5) the pedicles could be found in only 20% of cases whereas in the lower extremities (n = 11) 91% of pedicles were located. (P = 0.013). Peak flow within the free flaps was significantly higher in the lower extremity (50% of the peak flow of the common femoral artery) than in the upper extremity (5% of the peak flow of the common femoral artery, P = 0.013). This study demonstrated that non-innervated free muscle flaps in the extremities maintain the original muscle thickness, although lower extremity and latissimus dorsi flaps have a trend to be thicker. Most pedicles of free muscle flaps in the upper extremities could not be located by ultrasound. However, flaps in the lower extremities most often have patent pedicles and also more vigorous intramuscular blood flow.

Adolescent

Interferon-beta downregulates expression of VLA-4 antigen and antagonizes interferon-gamma-induced expression of HLA-DQ on human peripheral blood monocytes.

We have studied the effect of recombinant human IFN-beta on the basal and IFN-gamma-induced expression of adhesion molecules and class II MHC antigens on human peripheral blood monocytes and on ICAM-1 (intercellular adhesion molecule-1) expression of a human umbilical vein endothelial cell line (EAhy 926). We show that IFN-beta downregulates both basal and IFN-gamma-induced expression of VLA-4 (very late activation antigen-4) antigen on monocytes, but has no effect on the expression of CD11a, CD11b, CD11c, L-selectin, CD18, ICAM-1, beta 1-integrin or CD44 on monocytes or ICAM-1 on EAhy 926 cells. We also show that IFN-beta antagonizes the IFN-gamma-induced expression of HLA-DQ-antigen, but not HLA-DR or HLA-DP antigens on monocyte surface. These findings may partially explain the beneficial effect of IFN-beta in multiple sclerosis, since VLA-4-antigen is critical for leukocyte recruitment into inflamed brain and downregulation of HLA-class II expression diminishes antigen presenting capacity of monocytes.

Cells, Cultured