Biomedical subjects

M Lotz

Publications and source records attributed to M Lotz.

At least 91 records · Page 5Linked to original sources

PubMed1994

Integrin expression by human articular chondrocytes.

OBJECTIVE: To perform a comprehensive analysis of the integrin forms expressed by normal human articular chondrocytes. METHODS: Cartilage sections and collagenase-released chondrocytes were probed with a comprehensive panel of integrin isoform-specific monoclonal antibodies (MAb), using in situ immunohistochemistry techniques, indirect immunofluorescence and flow cytometry, and immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: Chondrocytes in cartilage sections reacted with MAb specific for the alpha 5, alpha v, and beta 1 integrin subunits and the alpha v beta 3 and alpha v beta 5 heterodimers. They also reacted with a polyclonal antibody specific for the intracytoplasmic portion of the alpha 1 subunit. MAb specific for the alpha v subunit reacted more strongly with chondrocytes near the articular surface than with those in deeper layers of cartilage, and the alpha v beta 3-specific MAb reacted exclusively with chondrocytes within the most superficial 30 microns of cartilage. Flow cytometric analysis and SDS-PAGE analysis of immunoprecipitates prepared from extracts of cell-surface radioiodinated chondrocytes confirmed the above observations, and additionally revealed the presence of the alpha 3 beta 1 integrin. CONCLUSION: Normal human articular chondrocytes prominently display substantial quantities of the alpha 1 beta 1, alpha 5 beta 1, and alpha v beta 5 integrin heterodimers, as well as lesser quantities of the alpha 3 beta 1 and alpha v beta 3 heterodimers. The alpha v subunit-containing integrins are detected more readily on the more superficial chondrocytes than on chondrocytes deep within cartilage. These observations provide the basis for analysis of the role of chondrocyte integrins in cartilage homeostasis and in the pathogenesis of joint diseases.

Adult↗

PubMed1994

Growth factor responsiveness of human articular chondrocytes: distinct profiles in primary chondrocytes, subcultured chondrocytes, and fibroblasts.

The objectives of this study were to establish a growth factor response profile for adult human articular chondrocytes, to determine whether this is unique for chondrocytes or influenced by the differentiation status of the cells, and to characterize growth factor interactions. It is shown that transforming growth factor-beta (TGF-beta) is the most potent mitogen among a variety of factors tested. All three isoforms of TGF-beta caused similar dose-dependent increases in chondrocyte proliferation. Other members of the TGF-beta family, including bone morphogenetic protein 2B (BMP2B), activin, and inhibin, did not detectably increase chondrocyte proliferation. Platelet-derived growth factor-AA (PDGF-AA), basic fibroblast growth factor (bFGF), and insulin-like growth factor 1 (IGF-1) also stimulated proliferation but were less effective than TGF-beta. In contrast to findings with other cell types, the effects of TGF-beta on chondrocyte proliferation were not dependent on the endogenous production of PDGF. The cytokines Interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) gave no stimulation, but IL-1 inhibited chondrocyte proliferation induced by TGF-beta or serum. This response profile was characteristic for primary chondrocytes from human adults and distinct from subcultured (dedifferentiated) chondrocytes or skin fibroblasts. The latter preferentially responded to PDGF, and IL-1 caused greater increases in proliferation than TGF-beta. In summary, these results describe growth factor responses that are characteristic for chondrocytes and provide a basis for the analysis of changes in chondrocyte growth proliferation that occur in aging and tissue injury.

Cartilage↗

PubMed1994

Neuropeptide Y is an inducible gene in the human immune system.

This study reports on neuropeptide Y (NPY) mRNA expression in human peripheral blood mononuclear cells (PBMC) and lymphoid tissues. By reverse transcription polymerase chain reaction (RT-PCR) it is shown that activated human PBMC of normal blood donors expressed the NPY gene. The PCR products had the expected size and Northern blotting demonstrated the presence of the 0.8-kb NPY mRNA. To define the subpopulations of mononuclear cells expressing this neuropeptide, purified monocytes, B cells and T cells were stimulated with specific activators. Monocytes and in vitro matured macrophages expressed NPY mRNA in response to phorbol myristate acetate (PMA). B lymphocytes expressed NPY mRNA following stimulation with antibody to surface immunoglobulin and PMA. In order to analyze whether these cell types express NPY under physiological conditions in vivo, human bone marrow, tonsil and thymus were analyzed. In situ hybridization of bone marrow revealed a small number of cells containing high levels of NPY mRNA which was also detected in RNA extracts of human thymus and tonsil. In summary, NPY is an inducible gene in human lymphocytes and monocytes and it is expressed at sites where these cells are activated in vivo.

Animals↗

PubMed1994

Anadamide, an endogenous cannabinoid receptor agonist inhibits lymphocyte proliferation and induces apoptosis.

This study examined the immunoregulatory effects of anadamide, the recently identified first endogenous cannabinoid receptor ligand. Anadamide caused dose-dependent inhibition of mitogen-induced T and B lymphocyte proliferation. Its potency was 3- and 10-fold less than that of the synthetic cannabinoids delta 8-tetrahydrocannabinol (delta 8-THC) and CP55940, respectively. Anadamide effects on DNA synthesis in T and B lymphocytes occurred rapidly as exposure of the cells during the final 4 h of culture was sufficient to achieve > 40% inhibition. Low doses of anadamide which caused significant inhibition of lymphocyte proliferation caused DNA fragmentation as demonstrated by immunohistochemistry, FACS analysis and Southern blotting. Apoptosis was also induced by high concentrations of delta 8-THC, but not by CP55940. Brain and peripheral cannabinoid receptor mRNA was expressed in PBMC with varying levels between individual donors. In summary, these findings demonstrate immunosuppressive effects of anadamide which are associated with inhibition of lymphocyte proliferation and the induction of cell death by apoptosis.

Adjuvants, Immunologic↗

PubMed1994

Interleukin-6 and interstitial cystitis.

We analyzed the presence of the cytokine interleukin-6 in urine samples from interstitial cystitis patients. Interleukin-6 was significantly elevated in patients with interstitial cystitis (169.29 +/- 90.81 pg./ml. versus 34.8 +/- 6.35 pg./ml. in controls). Representative urine samples were analyzed with specific antibody to interleukin-6 and greater than 80% of the biological activity was neutralized. These cytokine measurements were then compared with clinical parameters and interleukin-6 levels correlated positively with the pain scores. Studies on the potential cellular origin of interleukin-6 showed increased levels in spontaneously voided urine but not in ureteral urine, which was collected during cystoscopy, suggesting that interleukin-6 is the product of activated cells in the bladder. This finding is supported by in situ hybridization analyses, which showed that interleukin-6 messenger ribonucleic acid expressing cells are located in the interstitium and epithelial layer, and within blood vessels. The implications of these findings for interstitial cystitis pathogenesis are discussed.

Base Sequence↗

PubMed1994

Activation of urinary kallikrein in patients with interstitial cystitis.

A potential pathophysiological role for the urinary kallikrein-kinin system is suggested by the prominent symptoms of bladder pain and urinary frequency in interstitial cystitis. Kallikrein activity in the urine of 84 patients with interstitial cystitis and 33 normal volunteers was determined by cleavage of the synthetic substrate Val-Leu-Arg-pNA. Interstitial cystitis patients had significantly higher levels of kallikrein activity than did the normal volunteers. Kallikrein activity was correlated with symptoms of bladder pain and voiding frequency. The percentage of total urinary kallikrein in the active form correlated with active kallikrein levels and was also increased in interstitial cystitis patients, particularly those with higher levels of pain. Patients who underwent hydrodistention and subsequently experienced relief from the bladder symptoms had a decrease in urinary kallikrein levels, whereas patients who failed to improve following hydrodistention did not.

Adult↗

PubMed1994

The inducible production of nitric oxide by articular cell types.

Nitric oxide (NO) may play a role in tissue remodeling associated with arthritis. The articular cell sources of human inducible NO synthesis, however, have not been defined. This study demonstrates that human articular chondrocytes in primary or organ culture, but not synovial fibroblasts, produce NO in response to catabolic cytokines such as interleukin-1 (IL-1). As measured by the accumulation of NO2- in culture medium, NO production by IL-1-stimulated chondrocytes was inhibited by the NO synthase inhibitor Ng-monomethyl-L-arginine (NMA) and dependent on the presence of exogenous L-arginine. Other inflammatory cytokines such as tumor necrosis factor, but not transforming growth factor-beta, induced chondrocyte NO synthesis. The stimulation of NO synthesis required both RNA and protein synthesis. Chondrocytes isolated from cartilage derived from osteoarthritic patients also produced large amounts of NO in response to IL-1. In beginning to define potential effects of NO on chondrocyte function, it is shown that IL-1 induced an increase in cyclic guanosine monophosphate (cGMP) which was inhibited by NMA. In summary, these results demonstrate that cytokine-induced production of NO is a response of human articular chondrocytes but not of synovial fibroblasts. A potential role of NO in cytokine-induced tissue remodeling in the joint is provided by the induction of cGMP.

Cartilage, Articular↗

PubMed1994

HIV-1 transactivator protein Tat induces proliferation and TGF beta expression in human articular chondrocytes.

The human immunodeficiency virus-1 (HIV-1) protein Tat binds to cell surface antigens and can regulate cellular responses. Tat has similar immunosuppressive effects as transforming growth factor-beta (TGF beta) and both inhibit lymphocyte proliferation. TGF beta is expressed by primary human articular chondrocytes and is their most potent growth factor. The present study analyzed the interactions of TGF beta and HIV Tat in the regulation of human articular chondrocytes. Synthetic or recombinant full-length Tat (1-86) induced chondrocyte proliferation and this was of similar magnitude as the response to TGF beta. Tat peptides that did not contain the RGD motif had similar chondrocyte stimulatory activity as full-length Tat. Among a series of Tat peptides, peptide 38-62 which contains the basic domain was the only one active, suggesting that this region is responsible for the effects on chondrocyte proliferation. Full-length Tat and peptide 38-62 synergized with TGF beta and induced proliferative responses that were greater than those obtained with any combination of the known chondrocyte growth factors. Further characterization of the interactions between Tat and TGF beta showed that Tat increased synthesis and TGF beta activity and TGF beta 1 mRNA levels. The stimulatory effects of Tat and peptide 38-62 on chondrocyte proliferation were reduced by neutralizing antibodies to TGF beta and by TGF beta antisense oligonucleotides. These results identify a virally encoded protein and a synthetic peptide derived from it as novel and potent chondrocyte growth stimuli which act at least in part through the induction of TGF beta.

Base Sequence↗

PubMed1994

Organic factors and the clinical features of late paranoid psychosis: a comparison with Alzheimer's disease and normal ageing.

The diagnostic allocation and aetiological basis of paranoid psychoses with late onset is controversial. We examined the clinical features of patients with a diagnosis of paranoid psychosis and we compared their cranial computed tomography (CT) scans and electroencephalographic (EEG) recordings with findings from matched samples of patients with Alzheimer's disease and non-demented elderly controls. During a 5-year period, 81 patients (15 men and 66 women) with a diagnosis of paranoid psychosis and onset after age 50 were referred to our Institute. They represent 5.4% of the patients older than 50 admitted during the same period. More than half of these patients had first-rank symptoms. The ventricles, anterior and sylvian fissures of the paranoid group were larger than in non-demented controls but smaller than in Alzheimer's disease. The posterior dominant alpha EEG rhythm was slower than in normal aging and faster than in Alzheimer's dementia. If paranoid patients with first-rank symptoms were distinguished from the ones without, the former had less severe brain atrophy and faster posterior dominant rhythm, although they received higher doses of neuroleptics. This could be explained by the existence of at least 2 subgroups of late paranoid psychosis: late-onset schizophrenia and organic paranoid syndrome, the former characterized by first-rank symptoms and less severe brain atrophy, the latter by more severe EEG and CT scan changes with a closer resemblance to degenerative brain disease.

Aged↗

PubMed1994

Stimulation of HIV replication in mononuclear phagocytes by leukemia inhibitory factor.

This study examined the effects of leukemia inhibitory factor (LIF) on human immunodeficiency virus (HIV) replication in mononuclear phagocytes (MNP). LIF induced a dose-dependent increase in p24 antigen production in the chronically infected promonocytic cell line U1. The magnitude and time kinetics of the LIF effects were similar to interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF), other cytokines known to induce HIV replication in this cell line. To characterize mechanisms responsible for these LIF effects, levels of HIV mRNA, activation of the DNA binding protein nuclear factor (NF)-kB, signal transduction pathways, and potential interactions with other cytokines were analyzed. LIF increased steady-state levels of HIV mRNA at 2.0, 4.3, and 9.2 kB. This was detectable by 24 h and persisted until 72 h. The DNA binding protein NF-kB is a central mediator in cytokine activation of HIV transcription. NF-kB levels were higher in unstimulated U1 cells as compared to the parent cell line U937. In both cell lines LIF increased NF-kB activity. Induction of NF-kB and HIV replication by cytokines are at least in part dependent on reactive oxygen intermediates. The oxygen radical scavenger N-acetyl-L-cysteine, but not an inhibitor of nitric oxide synthase, inhibited LIF-induced HIV replication. LIF induces the production of other cytokines in monocytes but its effects on HIV replication were not inhibited by antibodies to IL-1, TNF, or IL-6. These results identify LIF as a stimulus of HIV replication.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗

PubMed1993

Protein tyrosine kinase activation is required for lipopolysaccharide induction of cytokines in human blood monocytes.

Bacterial LPS induce production of cytokines such as IL-1, IL-6, and TNF in mononuclear phagocytes, and this represents a central component in the pathogenesis of septic shock syndrome. However, the mechanisms by which LPS activates these cells to express cytokines are not completely characterized. The present study addressed the role of different protein kinases in the LPS induction of cytokines. It is shown that LPS induced a 12- to 16-fold increase in IL-1 beta, IL-6, and TNF-alpha mRNA levels, and this was completely or more than 80% blocked by the protein tyrosine kinase specific inhibitors herbimycin A and genistein at the concentrations of 1.7 and 37 microM, respectively. Protein kinase C inhibition by staurosporine reduced LPS induction of TNF-alpha, whereas it had no effects on IL-6 and IL-1 beta. Inhibition of protein kinase A by H89 reduced IL-6 mRNA levels but did not detectably change IL-1 beta or TNF-alpha mRNA levels. In contrast, LPS did not increase leukemia inhibitory factor mRNA, which was constitutively expressed and not significantly reduced by these inhibitors. In addition to cytokine mRNA levels, LPS-induced IL-6 protein synthesis and IL-6 bioactivity were also reduced to baseline levels by the PTK inhibitors herbimycin A and genistein. Both PTK inhibitors also reduced the LPS activation of nuclear factor-kappa B (NF-kappa B), which is a transcription factor involved in the expression of cytokine genes such as IL-6 and TNF-alpha. The activation of NF-kappa B was also reduced by H89, whereas staurosporine had no effect on this response. In summary, these findings suggest that protein kinase C and protein kinase A appear to have selective effects in the LPS induction of cytokines, whereas PTK is required for LPS induction of a broad spectrum of cytokines and NF-kappa B activation in monocytes.

Base Sequence↗

PubMed1993

A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family.

A 1.4-kb full-length cDNA was isolated from a library constructed from activated human T-cell leukemia virus type 1-transformed human T-lymphocytes. Sequence analysis identified this cDNA as a new member of the human nerve-growth-factor receptor/tumor-necrosis-factor receptor family and as the potential human homologue of the murine sequence, 4-1BB. The gene encodes three cysteine-rich motifs in the extracellular domain which are characteristic of this receptor family, a transmembrane region and a short N-terminal cytoplasmic portion which contains potential phosphorylation sites.

Amino Acid Sequence↗

PubMed1993

TSG-6: a TNF-, IL-1-, and LPS-inducible secreted glycoprotein associated with arthritis.

TSG-6 (TNF-stimulated gene 6) was originally discovered by differential screening of a cDNA library prepared from TNF-stimulated human diploid FS-4 fibroblasts. We show that the 35-kDa protein encoded by TSG-6 was undetectable in the medium of untreated FS-4 cultures, whereas its production reached approximately 1400 and 700 ng/10(6) cells after 24-h treatment with IL-1 or TNF, respectively. Stimulation of TSG-6 protein and mRNA levels was also demonstrated in normal human mononuclear cells by treatment with TNF and, especially, by LPS. In view of the inducibility of TSG-6 by inflammatory cytokines and its earlier demonstrated affinity for hyaluronan, we examined the presence of TSG-6 protein in the synovial fluids from patients with various forms of arthritis. TSG-6 protein was undetectable in the joint fluids of persons with no known history of arthritis, but high levels of TSG-6 oere demonstrated in the synovial fluids of a majority of arthritis patients. TSG-6 protein was also detected in the sera of some of the arthritis patients, albeit at concentrations that were less than in the joint fluids. To investigate the source of TSG-6 in the synovial fluids, we examined the production of TSG-6 protein in cultures of synovial cells. Synoviocytes from rheumatoid arthritis patients produced TSG-6 protein constitutively, and this production was increased by treatment with TNF or IL-1, but not with TGF-beta. Steady-state levels of TSG-6 mRNA were also increased in synoviocytes after treatment with TNF or IL-1. The presence of high levels of TSG-6 protein in the synovial fluids of arthritis patients and its inducibility by inflammatory cytokines in fibroblasts, mononuclear cells, synoviocytes, and chondrocytes suggest a role for TSG-6 in arthritis and inflammation.

Adolescent↗

PubMed1993

Interleukin-11, an inducible cytokine in human articular chondrocytes and synoviocytes, stimulates the production of the tissue inhibitor of metalloproteinases.

This study on the regulation of interleukin (IL)-11 expression in human connective tissue cells shows that IL-11 expression is not restricted to cells of hematopoietic origin but can also be induced in articular chondrocytes and synoviocytes. IL-11 mRNA was induced in chondrocytes in response to transforming growth factor (TGF)-beta 1 and IL-1 beta. Stimulation with IL-6 or growth factors, such as basic fibroblast growth factor, leukemia inhibitory factor, and platelet-derived growth factor-AA, had only weak or no detectable effects. Activation of protein kinase C by phorbol esters and inhibition of protein synthesis by cyclohexamide increased IL-11 transcripts, whereas calcium ionophore A23817 or dibutyryl cyclic AMP had no effect. Immunoprecipitations revealed the synthesis of IL-11 protein in response to TGF-beta 1, IL-1 beta, as well as phorbol 12-myristate 13-acetate, and a synergistic action of TGF-beta 1 and IL-1 beta was observed. Similar findings on IL-11 expression were made in synoviocytes. Analysis of effects on cell function showed that IL-11 stimulated the production of the tissue inhibitor of metalloproteinases in chondrocytes and synoviocytes but did not affect chondrocyte proliferation or increase stromelysin activity. These results suggest that IL-11 does not contribute to connective tissue degradation but conversely induces protective effects in joint tissue.

Cartilage, Articular↗

PubMed1993

IL-1 beta and IL-6 selectively induce transforming growth factor-beta isoforms in human articular chondrocytes.

Transforming growth factor-beta (TGF-beta) plays an important role in homeostasis of connective tissues, but regulation of its expression in mesenchymal cells is not well characterized. This study examines the effects of the cytokines IL-1 beta and IL-6 on expression of TGF-beta isoforms in human articular chondrocytes. IL-6 caused a fivefold increase, in the secretion of TGF-beta bioactivity by primary chondrocytes, whereas IL-1 beta showed only marginal stimulatory effects. Analysis by Northern blotting showed that IL-6 induced TGF-beta 1 gene expression but had no detectable effect on TGF-beta 2 mRNA levels and marginally increased TGF-beta 3 mRNA. However, IL-1 inhibited TGF-beta 1 mRNA expression induced by serum. In contrast, IL-1 beta strongly and selectively upregulated the TGF-beta 3 isoform. To determine whether this differential effect of IL-1 beta resulted in a corresponding change in protein synthesis, chondrocytes were metabolically labeled and analyzed by immunoprecipitation. IL-1 beta selectively induced TGF-beta 3 protein synthesis but reduced synthesis of the TGF-beta 1 and TGF-beta 2 isoforms. Consistent with the effects on TGF-beta 1 mRNA, IL-6 increased the synthesis of TGF-beta 1. These differential effects of the cytokines IL-1 beta and IL-6 provide new insight into the regulation of TGF-beta expression and may represent a protective mechanism against cytokine-induced connective tissue catabolism.

Adult↗

PubMed1993

TGF beta and HIV infection.

TGF beta is a cytokine which is involved with the regulation of different aspects of host defense responses to injury. Overexpression of TGF beta can lead to the conversion of its protective functions to pathogenetic manifestations. TGF beta is a potent factor in promoting anabolic aspects in connective tissue metabolism, and uncontrolled production of TGF beta has been associated with the development of fibrosis. With respect to its effects on immune and inflammatory responses, TGF beta is an important endogenous immunosuppressive factor which physiologically may protect the organism from tissue damage caused by chronic activation of leukocytes. As a result of overproduction in HIV infection, this function of TGF beta can contribute to noncytopathic mechanisms of immunodeficiency. TGF beta is involved with several aspects of HIV disease and promotes virus replication and spreading through multiple distinct mechanisms. It directly stimulates virus replication in infected monocytes and peripheral blood mononuclear cells under certain in vitro conditions. It may stimulate the production of other cytokines that enhance virus replication and it may be the mediator of other HIV-stimulating agents such as cocaine. It enhances recruitment of mononuclear phagocytes as cells susceptible to virus infection. Through its profound and broad inhibitory effects on different antiviral defense mechanisms, it facilitates more rapid progression of virus infection and increases susceptibility to opportunistic infections and malignancies. Although these findings are largely based on in vitro systems, the demonstration of TGF beta overexpression in HIV-infected patients supports the notion that this cytokine is an important pathogenetic mediator in HIV infection and its associated diseases. Therapeutic strategies to interfere with these functions of TGF beta are the development of TGF beta-neutralizing antibodies and soluble TGF beta-binding proteins and receptors as well as approaches directed at reducing TGF beta gene expression.

Animals↗

PubMed1993

Systemic immunological effects of cytokine genes injected into skeletal muscle.

Somatic gene therapy is an interesting approach for the delivery of cytokines for prolonged periods. The present experiments show that direct injections into mouse skeletal muscle of cDNA expression vectors encoding interleukin 2 (IL-2), IL-4, or type beta 1 transforming growth factor (TGF-beta 1) induce biological effects characteristic of these cytokines in vivo. Mice injected intramuscularly with a vector encoding IL-2 had enhanced humoral and cellular immune responses to an exogenous antigen, transferrin, that was delivered at a separate site. These IL-2 effects were abolished by coadministration of a vector directing synthesis of TGF-beta 1. The TGF-beta 1 vector by itself depressed the anti-transferrin antibody response and caused an 8-fold increase in plasma TGF-beta 1 activity. The TGF-beta 1 plasmid injection did not cause muscle infiltration with monocytes or neutrophils and there was no evidence for fibrotic changes. Muscle injection with a cDNA encoding IL-4 selectively increased IgG1 levels but did not alter the cellular immune response to transferrin. In lupus-prone mice (MRL/lpr/lpr), injection with IL-2 expression vectors increased and TGF-beta 1 vectors decreased auto-antibodies to chromatin. These results demonstrate that intramuscular injection of cytokine genes, in the absence of infectious viral vectors, can regulate humoral and cellular immune responses in vivo.

Animals↗

PubMed1993

Retinoic acid inhibits interleukin-1-induced cytokine synthesis in human monocytes.

Retinoids are pluripotent morphogens whose effects on gene expression are mediated through specific intracellular receptors. They have certain anti-inflammatory effects in vivo, the basis of which is not clearly understood. To characterize mechanisms involved with potential anti-inflammatory actions of retinoids, we studied the effects of retinoic acid (RA) on cytokine production in human peripheral blood monocytes. RA differentially modulated the expression of interleukin-1 beta (IL-1 beta), IL-6, and IL-8 mRNAs depending on the inducing stimulus. While phorbol myristate acetate-induced IL-1 beta and IL-8 mRNA expression was increased by RA (IL-6 could not be induced by this pathway in monocytes), IL-1 beta-induced expression of IL-1 beta and IL-8 was markedly reduced and IL-6 gene expression was almost completely suppressed. Lipopolysaccharide (LPS)-induced cytokine synthesis was only slightly reduced and this required a longer preincubation (> 72 h) of monocytes with RA. IL-1-induced de novo synthesis of IL-6 protein and secretion of biologically active IL-6 were also inhibited by RA. The inhibition pattern of RA was different from that of dexamethasone, which inhibited both IL-1 and LPS effects. In summary, our data show that RA regulates monocyte cytokine expression selectively in response to the particular stimuli. Inhibition of IL-1 beta-induced cytokine expression provides a mechanism that can explain some of the anti-inflammatory effects of RA.

Base Sequence↗