[The role of helper t-cell subsets in infectious diseases and allergy].
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Cell Differentiation↗
Biomedical subjects
M Hurme
Publications and source records attributed to M Hurme.
Regulation of interleukin-1 beta production by glucocorticoids in human monocytes: the mechanism of action depends on the activation signal.
Glucocorticoids are known to downregulate interleukin-1 beta production in monocytic cells by two different mechanims: direct inhibition of the gene transcription and destabilization of the preformed interleukin-1 beta mRNA. Now we have examined the effect of the nature of the monocyte activating signal on these two inhibitory mechanims. When human monocytes were preincubated with dexamethasone for 1 hour and then stimulated either with bacterial lipopolysaccharide or phorbol myristate, it was found that dexamethasone inhibited the lipopolysaccharide-induced interleukin-1 beta protein production, but the phorbol myristate-induced production was increased 3-10 fold. This difference was also seen at the mRNA level. When dexamethasone was added to the cultures 3 hours after the stimulators, it clearly decreased the interleukin-1 beta mRNA levels regardless of the stimulator used (although the effect was clearly weaker on the PMA-induced mRNA). Thus these data suggest that the phorbol myristate-induced signal (prolonged protein kinase C activation?) cannot be inhibited by prior incubation with dexamethasone and it also protects the induced mRNA for the degradative action of dexamethasone.
Cells, Cultured↗
Retinoic acid enhances IL-1 beta expression in myeloid leukemia cells and in human monocytes.
We have examined the role of retinoic acid (RA), the biologically active metabolite of vitamin A, in expression of the IL-1 beta gene in the human myeloid leukemia cell line THP-1 and in human monocytes. Both protein kinase C-activating phorbol esters, e.g., PMA, and LPS induce IL-1 beta expression in these cells. Physiologic RA concentrations alone were not able to induce any IL-1 beta production, but they strongly enhanced the PMA-induced IL-1 beta protein production and mRNA accumulation in both human monocytes and in THP-1 cells. Nuclear run-off analysis revealed that the enhancing effect was at the transcriptional level. RA also slightly potentiated LPS-induced IL-1 beta expression in THP-1 cells but not in human monocytes. These data suggest that RA can be a strong up-regulator of IL-1 production, but its strength varies depending on the nature of the activating signal.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Restoration of patellofemoral congruity by combined lateral release and tibial tuberosity transposition as assessed by MRI analysis.
Twelve knees in eleven patients with subluxation or dislocation of the patella were assessed by MRI at 0, 10, 20 and 30 degrees of knee flexion, before and after vastus lateralis release and medial transplant of the tibial tuberosity. The preoperative position of the patella deviated the greatest from normal in 0-20 degrees of knee flexion. The operations were found to correct the lateral patellofemoral angle and the lateral patella tilt with or without quadriceps muscle contraction, but did not completely correct the marked preoperative lateral patellar displacement and tracking.
Adult↗
Clinical findings as outcome predictors in rehabilitation of patients with sciatica.
In rehabilitation of patients with sciatica, factors prognostic of long-term outcome could prove beneficial in interventions and in evaluating progress toward fitness or capacity for work. In this study results of physical examinations, carried out one year after hospital treatment for suspected lumbar intervertebral disc herniation, were related to outcome after five-years, as assessed by the categorization of occupational handicap of the International Classification of Impairments, Disabilities and Handicaps (ICIDH). The sample consisted of 276 patients admitted to hospital in the years 1980-1982. Based on established clinical indications 179 patients underwent lumbar disc surgery and the remaining 97 received further conservative treatment. One year after hospitalization a physician and physiotherapist examined the patients at the Rehabilitation Research Centre (RRC) of the Social Insurance Institution in Finland. In 1986 the patients returned to the RRC for further evaluation of their occupational handicap at that time. Stepwise logistic regression analysis showed that sensory deficits of legs, tenderness in lumbar extension, decreased repetitive trunk flexion performance (sit-up test), decreased lumbar lordosis and tightness of hamstrings were indicative of a poor outcome in the operated group. For the non-operated patients no statistically acceptable regression analysis model could be established.
Adult↗
Cyclic adenosine monophosphate decreases the secretion, but not the cell-associated levels, of interleukin-1 beta in lipopolysaccharide-activated human monocytes.
Interleukin-1 beta (IL-1 beta) is a cytokine produced mainly by activated monocytes though the mechanism by which it is released is still unknown. Elevation of intracellular cyclic adenosine monophosphate (cAMP) is considered an important down-regulative signal in the production of IL-1 beta in lipopolysaccharide (LPS)-induced monocytes. In this study we show that in LPS-activated human monocytes, elevated cAMP concentrations (induced by either prostaglandin E2, forskolin or dibutyrylcyclic AMP) affected specifically secretion of IL-1 beta; the amount of secreted IL-1 beta was clearly reduced whereas the cell-associated level remained unchanged. TNF-alpha, a normal secretory protein, was used as a control. Cyclic AMP also inhibited TNF production by monocytes, but the decrease was of the same magnitude in the extracellular and intracellular compartments. Thus, the down-regulative effect of cAMP on the production of these monokines is clearly different.
Bucladesine↗
Different activation signals are required for the expression of interleukin-1 alpha and beta genes in human monocytes.
The production and mRNA expression of IL-1 alpha and IL-1 beta by human monocytes was examined after two different stimuli, a protein kinase C (PKC) activator phorbol myristate acetate (PMA) and bacterial lipopolysaccharide (LPS). LPS induced production of high levels of both IL-1 alpha and IL-1 beta protein (quantitated with type-specific ELISA assays), while after PMA stimulation only IL-1 beta protein could be detected. The IL-1 alpha and IL-1 beta mRNA levels quantitated by Northern blotting were in line with the respective protein levels and nuclear run off analysis revealed that PMA did not activate the IL-1 alpha transcription. The production of the IL-1 alpha and IL-1 beta protein as well as the mRNA expression could be inhibited with protein kinase inhibitor H7, but not with HA1004, indicating that PKC activation is essential for the activation of these genes. Thus these data indicate that PKC activation alone is sufficient for the induction of the IL-1 beta gene, but some additional signals (provided by LPS) are required for the activation of the IL-1 alpha gene.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Social factors and outcome in a five-year follow-up study of 276 patients with sciatica.
Social factors of 179 operated and 97 non-operated patients one year after hospitalization due to low back pain and sciatica were tested by multi-variate regression analysis in relation to the five-year outcome evaluated according to the WHO Handicap Classification. For operated men a subjective working incapacity (relative risk RR = 4.6) and co-morbidity (RR = 2.7) predicted a poor outcome. For operated women the predictive factors were subjective working incapacity (RR = 3.2) and older age (RR = 1.9). For non-operated men an increased occurrence of occupational hazards (RR = 3.6) and for non-operated women co-morbidity (RR = 7.1) indicated a poor outcome.
Adult↗
CT five years after myelographic diagnosis of lumbar disk herniation.
Fifty-seven patients were examined with CT 5 years after primary myelography for disabling sciatica and suspected herniated lumbar disk. Forty were in an operated group, 22 with good and 18 with poor results evaluated by occupational handicap (21) 5 years after surgery. Seventeen patients had myelography indicating disk herniation, but were treated conservatively, 9 with good and 8 with poor result. Various spinal dimensions measured at CT did not correlate with outcome. Operated patients had narrower canals than others, and male canals were broader than those in females. Increased amount of scar tissue at L4 level correlated with poor result (p = 0.008). Operated patients with poor result had more advanced lateral stenosis than those treated conservatively (p less than 0.001). Patients with good result after operation had more degeneration observed on CT of erector spinae muscle than those treated conservatively with good outcome. Only 9% of operated patients did not have muscle degeneration. A tendency for more frequent recurrent disk herniations could be seen for conservatively treated patients. The narrowing of the spinal canal 5 years after operation did not correlate with the 5-year outcome.
Adult↗
Control of interleukin-1 beta expression by protein kinase C and cyclic adenosine monophosphate in myeloid leukemia cells.
We have examined the signal transduction pathways leading to the expression of the interleukin-1 beta (IL-1 beta) gene in human myeloid leukemia cells lines. Two cell lines representing different stages of differentiation were used (HL-60, promyelocytic, and THP-1, mature monocytic). In accordance with previous studies, it was observed that a protein kinase C (PKC) activator, phorbol myristate acetate (PMA), was a sufficient stimulus for induction of the IL-1 beta messenger RNA (mRNA) expression and IL-1 beta protein production in both of these cell lines. A structural analog of cyclic adenosine monophosphate (dbcAMP) or agents elevating the endogenous cAMP levels (prostaglandin E2, forskolin) were not alone able to induce IL-1 beta expression, but they strongly enhanced the PMA-induced IL-1 beta production and IL-1 beta mRNA accumulation. Nuclear run off analysis showed that this elevation in IL-1 beta mRNA levels was due to an increased rate of transcription. If dbcAMP was added 6 hours before PMA to the cultures, no enhancement in the IL-1 beta production was seen, implying that for this enhancing effect both of these signals must be present simultaneously. PKC inhibitor, H7, also blocked effectively the PMA plus dbcAMP induced IL-1 beta production, while the protein kinase A (PKA) inhibitor, HA1004, had no effect, suggesting that PKA activation is not involved in the mechanism of action of cAMP in this case. Collectively, the present findings show that cAMP-dependent signals can have a positive regulatory effect on the PKC-dependent activation of the IL-1 beta gene in cells derived from different stages of myeloid differentiation.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Growth inhibition caused by serum depletion induces differentiation, interleukin 1 receptor expression and interleukin 1 responsiveness in the HL-60 promyelocytic leukemia cell line.
The role of interleukin-1 (IL-1) was studied in the proliferation of promyelocytic HL-60 leukemia cells. When HL-60 cells were cultured in 10% fetal calf serum (FCS) containing medium IL-1 did not have any effect on the proliferation. In 1% FCS containing medium, the proliferation of HL-60 cells gradually decreased, but IL-1 was found to be clearly mitogenic for these cells. IL-1 did not function as an autocrine growth factor for HL-60 cells, since anti-IL-1 antibodies did not suppress the basal proliferation of these cells. IL-1 was also mitogenic for U937 but not for THP-1 cells. The suppression of HL-60 proliferation was found to be accompanied with monocytic differentiation as assessed by an increase in HLA-DR, CD11b and CD14 antigen expression. IL-1 could suppress this differentiation. HL-60 cells cultured in 1% FCS were found to express increased amounts of IL-1 receptors on the cell surface.
Antigens, Differentiation↗
Modulation of interleukin-1 beta production by cyclic AMP in human monocytes.
Elevation of cAMP has been considered to be an important downregulative signal in the production of interleukin-1(IL-1). This study demonstrates that this phenomenon is dependent on the signal used to activate the IL-1 production. The IL-1 beta production of lipopolysaccharide activated human monocytes was readily inhibited by dibutyryl cAMP. This took place without a significant change in the steady-state levels of IL-1 beta mRNA. By contrast, in PMA activated monocytes 100 microM dibutyryl cAMP increased in IL-1 beta production ca. 4-fold. The steady-state levels of IL-1 beta mRNA were also simultaneously increased.
Bucladesine↗
Both dendritic cells and monocytes induce autologous and allogeneic T cells receptive to interleukin 2.
Activation of resting T cells to proliferate is usually accompanied by their expression of interleukin 2 receptors (IL-2R) and secretion of (IL-2). We studied the mechanisms by which human blood-derived dendritic cells (DC) and monocytes induce IL-2R and stimulate IL-2 secretion in autologous and allogeneic mixed luecocyte reaction (auto- and allo-MLR, respectively). We found that only DC were fully effective as stimulator cells in MLR. DC stimulated both autologous and allogeneic T cells to express high-affinity IL-2R, secrete IL-2, and vigorously proliferate in MLR. The stimulatory properties of monocytes were more complicated: although they stimulated the proliferation in allogeneic MLR, the proliferation rates, duration, and amount of IL-2 secretion were different than in DC-induced MLR. Autologous T cells did not proliferate in response to monocytes, but were induced to express the low-affinity IL-2R. If the cultures were supplemented with exogenous recombinant IL-2, the proliferative responses to DC and monocytes in auto- and allo-MLR were of the same magnitude, indicating that the responsiveness to IL-2 was stimulated by both the stimulator cells. The stimulator cell number was important, since large numbers of monocytes, but not of DC, were suppressive to the proliferative responses. Thus, we concluded that the higher capacity of DC, as compared to monocytes, to stimulate T-cell proliferation is based primarily on the more efficient stimulation of IL-2 secretion.
Antibodies, Monoclonal↗
Human peripheral blood-derived dendritic cells do not produce interleukin 1 alpha, interleukin 1 beta, or interleukin 6.
Little is known about the non-antigen-specific signals delivered to T cells by dendritic cells (DC). Because several monocyte-derived factors like interleukins 1 alpha, 1 beta, and 6 (IL-1 alpha, IL-1 beta, and IL-6) enhance the T-cell proliferative responses, we studied the production of the above-mentioned cytokines by DC separated from human peripheral blood. The intracellular expression of the proteins (IL-1 alpha and IL-6) was studied at a single-cell level using an immunolabelling technique. The supernatants and cell lysates were studied with ELISA (IL-1 alpha and IL-1 beta). Northern blotting analysis was used to quantitate the mRNA levels. Several approaches were taken to stimulate the production of IL-1 alpha, IL-1 beta, and IL-6 by DC. These included the incubation of the DC in the presence of either LPS, rIL-1, or monoclonal anti-HLA-DR antibody, or the stimulation of cells with resting allogeneic T cells. None of the stimuli was able to induce the production of IL-1 alpha, IL-1 beta, or IL-6 by DC, whereas LPS-stimulated monocytes were strong producers of these mentioned cytokines and expressed the respective mRNA. Thus we concluded that IL-1 alpha, IL-1 beta, and IL-6 are primarily monocyte-derived factors and that these factors are not needed or produced during the activation of resting T cells by DC.
Animals↗
Effect of lateral release on patellar motion in chondromalacia. An MRI study of 11 knees.
Preoperatively and postoperatively, patellar motion in 11 knees with chondromalacia was analyzed by MRI at 0 degrees, 10 degrees, 20 degrees, and 30 degrees of knee flexion. The preoperative patellar position clearly deviated from normal at 0 degrees-10 degrees of knee flexion. The lateral release operation corrected this deviation.
Adult↗
[Growth factors and differentiation of hematopoietic cells].
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Animals↗
A prospective study of patients with sciatica. A comparison between conservatively treated patients and patients who have undergone operation, Part I: Patient characteristics and differences between groups.
Based on a prospective study on 342 sciatica patients examined with rhizography, the aim was to determine which factors others than the rhizography finding and the grade and duration of symptoms were related to the selection of patients to undergo operation. Compared with surgically treated patients, conservatively treated patients who did not undergo operation and who had pathologic rhizography findings had pessimistic attitudes to possible surgery, often expressed a desire to retire, and considered their work as physically stressful. The women in this group were older and had lower pain indices than women who underwent operation. Conservatively treated patients with negative rhizography had more severe occupational handicaps, minor expectations of possible surgery, physically more strenuous jobs requiring difficult physical positions, and lower indices for pain and ADL than did the operated patients. The social and ergonomic background problems are emphasized in sciatica patients conservatively treated after rhizography.
Adult↗
A prospective study of patients with sciatica. A comparison between conservatively treated patients and patients who have undergone operation, Part II: Results after one year follow-up.
The prospective study included 122 sciatica patients who had not undergone operation (NOPs) and 220 sciatica patients who had undergone operation (OPs); all had been examined by rhizography. The follow-up study was done on 110 (90%) of the NOPs and 212 (96%) of the OPs. The NOPs were divided into two groups: 30 patients with pathologic rhizography (PR) and 80 patients with negative rhizography (NR). Pain-, ADL-, and occupation-handicap indices showed that after the 1 year follow-up the OP group had the best result and the NR group the lowest result. The PR group had nearly as good a result as the OP group. Thus, sciatica patients are candidates for conservative therapy, even though they have pathologic findings in rhizography, if the symptoms are mild. To improve therapeutic outcome, more accurate diagnostic tools are needed to develop specific therapy especially for those sciatica patients with negative rhizography.
Adult↗