Arsenic induces interleukin-8 expression in cultured keratinocytes.
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Arsenic↗
Biomedical subjects
C L Yu
Publications and source records attributed to C L Yu.
The expression of cytokines by an established basal cell carcinoma cell line (BCC-1/KMC) compared with cultured normal keratinocytes.
A basal cell carcinoma (BCC) cell line (BCC-1/KMC) has recently been successfully established from a patient. The production of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6 and IL-8 was assessed in comparison with that of cultured normal keratinocytes. The mRNA expression of these cytokines was measured by a reverse transcriptase-polymerase chain reaction (RT-PCR) method and the protein production by an ELISA. The cultured BCC cells spontaneously secreted more IL-6 and IL-8 but less IL-1 than the keratinocytes after culture for 24 h at 37 degrees C. It is suggested that the increased expression of IL-6 and IL-8 may indicate the transformation of normal keratinocytes to locally aggressive BCC.
Basal Cell Carcinoma↗
UVB irradiation induces decreased expression of beta 2-adrenergic receptors in cultured keratinocytes.
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Cells, Cultured↗
Low-energy helium-neon laser irradiation stimulates interleukin-1 alpha and interleukin-8 release from cultured human keratinocytes.
Clinical observations have suggested that low-energy lasers might promote wound healing. Evidence suggests that He-Ne laser irradiation induces an increase in the rate of keratinocyte migration and proliferation as compared with nonirradiated controls in vitro. This study sought to determine whether He-Ne laser could induce cytokine production in cultured keratinocytes. The results revealed (i) a significant increase in interleukin-1 alpha and interleukin-8 production and their respective mRNA expression in He-Ne laser-treated groups as compared with nonirradiated controls, and (ii) under 1.5 joules/cm2 irradiation, this stimulating effect of He-Ne laser treatment is concentration-dependent. Because interleukin-1 alpha induces keratinocyte migration, this finding may partially explain the stimulatory effects on the motility of keratinocytes. As both interleukin-1 alpha and interleukin-8 provoke proliferation of keratinocytes, it is not unreasonable to propose that these two cytokines play a profound role in the enhancement of keratinocyte proliferation as a result of He-Ne laser irradiation. Our findings provide further evidence of enhanced wound healing at the cellular and molecular level as a result of the He-Ne laser.
Cells, Cultured↗
Increased excretion of tumor necrosis factor alpha and interleukin 1 beta in urine from patients with IgA nephropathy and Schönlein-Henoch purpura.
Urinary proteins (5 mg/ml) collected from a group of 16 patients including 13 with IgA nephropathy and 3 with Schönlein-Henoch purpura (SHP) and from a control group consisting of 6 patients with diabetic nephropathy, 5 patients with hypertensive nephrosclerosis, and 5 healthy hospital staff members were studied for the contents of interleukins (IL) 1 beta, 2, 4, 6, and 12 and tumor necrosis factor alpha (TNF-alpha). Eleven patient with IgA nephropathy or SHP (11/16) but only 1 of the controls (1/16) had TNF-alpha activity in urinary proteins (p < 0.01). The IL-1 beta activity exhibited a similar tendency but to a lesser extent (10 of 16 patients with IgA nephropathy or SHP vs. 2 of 16 with other conditions, p < 0.05). Conversely, the detection rates of IL-2, IL-4, and IL-6 in both groups were not significantly different. IL-12 was not found in any of the samples from both groups. Sera and nonpurified urine samples from the same individuals were also measured for cytokines. IL-1 beta, IL-2, IL-4, and IL-12 were absent in all these samples, but TNF-alpha was found in four of the serum samples from patients with IgA nephropathy. Urinary proteins (2 mg/ml) were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereby peptides of 52, 49, 45, 34, 30, and 11 kD could be demonstrated in the patients with IgA nephropathy or SHP. Urinary proteins (200 micrograms/ml from patients with IgA nephropathy or SHP exerted a mitogen-like effect on the normal human mononuclear cells, as demonstrated by 3H-thymidine incorporation. In addition, these urinary proteins (400 micrograms/ml) enhanced the proliferative activity of the cultured rat glomerular mesangial cells. The exaggerated proliferation of rat glomerular mesangial cells exerted by urine proteins from 2 patients with active disease was markedly suppressed after treatment with glucocorticoids/cyclophosphamide. These results suggest that patients with IgA nephropathy or SHP can excrete excessive amounts of TNF-alpha and IL-1 beta in the urine. The inconsistent presence of these two cytokines in urine and serum may indicate that they can be produced locally and that they are implicated in the development of mesangial inflammation and glomerular damage.
Adolescent↗
Understanding the molecular mechanism of dominant negative action of mutant thyroid hormone beta 1-receptors: the important role of the wild-type/mutant receptor heterodimer.
The clinical manifestations of patients with resistance to thyroid hormone result from inhibition of the functions of wild-type thyroid hormone receptors (wTRs) by the dominant negative effect of mutant TR beta 1 receptors (mTR beta 1). One of the proposed mechanisms by which mTR beta 1 exerts its dominant negative action is via formation of the putative inactive wTR beta 1/mTR beta 1 heterodimer. However, the nature of the wTR beta 1/mTR beta 1 heterodimer is poorly understood. The present study characterizes the wTR beta 1/mTR beta 1 heterodimer by electrophoretic mobility shift assay. The mutant TR beta 1 used was PV, which contains a frame shift mutation in the C-terminal part of TR beta 1 and has less than 1% of the T3 binding affinity of the wTR beta 1. Because of the difficulty in resolving wTR beta 1 and mutant PV dimers, we used a truncated wTR beta 1 in which the A/B domain was deleted (delta TR beta 1) to demonstrate the formation of the heterodimer on thyroid hormone response elements (TREs) in which the half-site binding motifs are oriented in an inverted repeat (F2), a direct repeat separated by four nucleotides (DR4), or an inverted repeat (Pal). Deletion of the A/B domain had no effect on the binding of T3 and TREs to wTR beta 1. In the presence of equal amounts of delta TR beta 1 and PV, three types of molecular complexes. delta TR beta 1 homodimer, delta TR beta 1/PV heterodimer, and PV homodimer bound to each TRE in a ratio of approximately 1:2:1. The identities of these complexes were confirmed by their ability to be supershifted by anti-TR beta 1 and/or anti-PV antibodies. delta TR beta 1/PV heterodimer formation varied with different TREs. The ratio of apparent affinity constant (Ka) in the binding of delta TR beta 1/PV to TREs was F2:DR4:Pal = approximately 6:2:1. The effect of T3 on delta TR beta 1/PV heterodimer formation was TRE dependent. No T3-induced dissociation was observed for the delta TR beta 1/PV heterodimer when bound to F2 and Pal. In contrast, the delta TR beta 1/PV heterodimer bound to DR4 was dissociated by T3 with an ED50 of 3.9 +/- 0.9 nM. The T3-induced dissociation of delta TR beta 1 homodimer bound to F2, DR4, and Pal had ED50 values of 4.1 +/- 1.2, 1.3 +/- 0.3, and more than 100 nM, respectively. By transfection assays, the dominant negative action of PV was found to be TRE dependent with the rank order of F2 >> Pal > ME (a DR4-like TRE in the rat malic enzyme gene). Taken together, these results indicate a strong correlation between wTR beta 1/mTR beta 1 heterodimer formation and the dominant negative potency of PV. These results suggest that the wTR beta 1/mTR beta 1 heterodimer could play an important role in the dominant negative action of mTR beta 1.
Animals↗
Bilateral carpal tunnel syndrome secondary to tophaceous compression of the median nerves.
A 65-year-old man with long-term gouty arthritis developed bilateral carpal tunnel syndrome. At surgery a chalky substance, which showed negative birefringence on polarized microscopy, was found infiltrating around the intensely inflamed transverse carpal ligaments. In differential diagnosis of carpal tunnel syndrome, tophaceous compression over the median nerve should be taken into consideration.
Arthritis, Gouty↗
Osteochondroma in a patient with juvenile ankylosing spondylitis associated with idiopathic thrombocytopenic purpura and alpha thalassemia.
An unusual combination of osteochondroma, ankylosing spondylitis, thalassemia alpha, and thrombocytopenia was found in a young man who had once been an amphetamine addict. The association of these settings might have been coincidental but it cannot be excluded that the preexisting inflammatory processes or tissue destruction in the latter 3 diseases might have rendered the patient prone to the development of osteochondroma.
Adult↗
The expression of acidic ribosomal phosphoproteins on the surface membrane of different tissues in autoimmune and normal mice which are the target molecules for anti-double-stranded DNA antibodies.
Affinity-purified polyclonal anti-double-stranded DNA (anti-dsDNA) antibodies from patients with systemic lupus erythematosus (SLE) exert a cytostatic effect on cultured rat glomerular mesangial cells (MC). The cognate antigens expressed on the surface of MC have been proved to be acidic ribosomal phosphoproteins (P proteins) in our previous study. The mesangial cytostatic effect of anti-dsDNA antibodies is attributed to the cross-reactivity of the antibodies with membrane-expressed P proteins, but not to the effect of minute amounts of anti-ribosomal P proteins antibodies contained in the anti-dsDNA preparations. Immunofluorescence staining of the native cells demonstrated that anti-dsDNA antibodies bound to the surface of rat mesangial cells, rat brain astrocytes (RBA-1) and mouse fibroblasts (3T3). Anti-dsDNA antibodies also exert potent cytostatic effects on these cells in a dose-dependent manner. In addition, the plasma membranes of different cell lines and tissues from normal and autoimmune mice were isolated and probed by anti-dsDNA antibodies in Western blot analysis. We found the actively proliferating cells such as MC, RBA-1 and 3T3 may express both P0 (38,000 MW) and P1 (19,000 MW) on the surface membrane. In addition, the kidney, liver and spleen from either autoimmune MRL-lpr/lpr or BALB/c mice may constantly express P0 protein, but the expression of P1 is inconsistent. In contrast, brain and muscle from either mice failed to express P proteins on their surface. Unexpectedly, a high molecular weight substance (larger than 205,000 MW) with unknown nature appears in the membrane of brain and muscle tissues in both mice. Immunoprecipitation of the surface-biotinylated MC-lysate by anti-dsDNA antibodies further confirmed that P1 (19,000 MW) and P2 (17,000 MW) are really expressed on the cell surface. These results suggest that P proteins expressed on the surface of different tissues become the targets for anti-dsDNA antibodies mediating pleomorphic tissue damage in patients with SLE.
Animals↗
The cytotoxic effect of neonatal lupus erythematosus and maternal sera on keratinocyte cultures is complement-dependent and can be augmented by ultraviolet irradiation.
To elucidate the role of autoantibodies and ultraviolet (UV) exposure in the pathogenesis of the skin lesions in neonatal lupus erythematosus (NLE), keratinocytes were cultured, as the target cells, from a patient with NLE and from a normal neonate. We demonstrated that the expression of nuclear/cytoplasmic Ro/SSA and La/SSB molecules on to the surface of NLE keratinocytes occurred to a much greater extent than that on normal keratinocytes. A dose of 200 mJ/cm2 UVB irradiation on NLE keratinocytes induced a 2.5-3-fold increase in Ro/SSA and La/SSB expression compared to non-irradiated cells. Sera derived from both the NLE patient and from his mother exhibited a cytotoxic effect on NLE keratinocytes, but not on control cells, in the presence of complement. Furthermore, the cytotoxicity of the sera was enhanced on UVB-irradiated NLE keratinocytes, whereas it had no cytotoxic effects on UVB-irradiated control cells. This suggests that the abnormal expression of both Ro/SSA and La/SSB on the surface membrane of NLE keratinocytes induces the autoantibodies and complements to injure the cells. This complement-mediated cytotoxic effect can be augmented by UV irradiation, a concept not incompatible with the exacerbation of the skin eruption in sun-exposed skin sites.
Antigens, Surface↗
Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein.
Cytokines and growth factors induce tyrosine phosphorylation of signal transducers and activators of transcription (STATs) that directly activate gene expression. Cells stably transformed by the Src oncogene tyrosine kinase were examined for STAT protein activation. Assays of electrophoretic mobility, DNA-binding specificity, and antigenicity indicated that Stat3 or a closely related STAT family member was constitutively activated by the Src oncoprotein. Induction of this DNA-binding activity was accompanied by tyrosine phosphorylation of Stat3 and correlated with Src transformation. These findings demonstrate that Src can activate STAT signaling pathways and raise the possibility that Stat3 contributes to oncogenesis by Src.
Animals↗
Role of tumor necrosis factor-alpha in the regulation of activated synovial T cell growth: down-regulation of synovial T cells in rheumatoid arthritis patients.
To characterize the role of tumor necrosis factor (TNF)-alpha in regulating synovial T cell growth, cell cycle progression associated with TNF-alpha in mitogen-activated synovial T cells of patients with rheumatoid arthritis (RA) were analyzed. After mitogen stimulation, the majority of synovial T cells in RA patients accumulated in S-phase. Anti-human TNF-alpha monoclonal antibody and soluble recombinant human TNF receptor (rhTNFR) can block S-phase accumulation. Furthermore, synovial fluid (SF) from RA patients was able to inhibit the proliferation of these S-phase-accumulated T cells. These data indicate that TNF-alpha could regulate activated synovial T cell growth by driving them into S-phase. Combined with the activities of other components of SF, TNF-alpha seems to play an important role in down-regulating activated synovial T cells in RA patients. In addition, the elevated level of soluble TNFR in the SFof disease-active RA patients is believed to be associated with the promotion of synovial T cell responses.
Arthritis, Rheumatoid↗
Suppression of proteinuria and prolongation of survival in MRL-lpr/lpr mice treated with sulphasalazine.
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Animals↗
Defective spontaneous and bacterial lipopolysaccharide-stimulated production of interleukin-1 receptor antagonist by polymorphonuclear neutrophils of patients with active systemic lupus erythematosus.
Interleukin-1 receptor antagonist (IL-1ra) binds competitively to IL-1 receptors but does not transduce the signal which blocks the biological activities induced by IL-1. In this study, polymorphonuclear neutrophils (PMN) and mononuclear cells (MNC) from the patients with active systemic lupus erythematosus (SLE) (n = 11), inactive SLE (n = 13) and normal individuals (n = 13) were compared for the IL-1ra producing capacity of these cells. PMN and MNC at a concentration of 1 x 10(6) cells/ml were incubated with medium alone (spontaneous) or stimulated with lipopolysaccharide (LPS, 100 ng/ml) for 24 h. The IL-1ra concentration in the supernatants was quantified by ELISA method. Both spontaneous and LPS-stimulated production of IL-1ra by PMN, but not by MNC, of active SLE were significantly lower than that of inactive SLE or normal groups. Prednisolone (1 and 5 micrograms/ml) did not change the production of IL-1ra by normal PMN either spontaneously or LPS-stimulation in in vitro study. Moreover, the IL-1ra producing capacity of PMN in seven active SLE on admission and after intensive immunosuppressive treatment was measured. These results suggest that the defective IL-1ra production by SLE-PMN is relevant to disease activity and may be regarded as a new indicator of disease activity in patients with active SLE.
Adolescent↗
A dominant human leucocyte antigen DR4-Dw15 restricted mycobacterial 65 kDa antigen-specific T-cell immunity in Chinese patients with rheumatoid arthritis.
The human leucocyte antigen DR4-associated immune responses to Mycobacterium tuberculosis 65 kDa heat shock protein were considered to be relevant to the pathogenesis of rheumatoid arthritis (RA). In the Chinese population, DR4-Dw15 was found to be the predominant DR4 subtype in RA. To further define the immune responses associated with DR4-Dw15 molecules, the proliferative responses of peripheral (PBMC) and synovial mononuclear cells (SFMC) to mycobacterial 65 kDa antigen were evaluated. The SFMC of all of our RA patients responded significantly to 65 kDa mycobacterial antigen. The responses of PBMC to this antigen in RA were much lower than those of SFMC. Our results further indicated that relatively low numbers of peripheral antigen-specific T-cells, but not incompetence of peripheral antigen presenting cells, might be related to the observed low responsiveness to 65 kDa antigen in PBMC of RA patients. Of utmost importance, DR4-Dw15 was proved to be one of the major restrictive molecules in mycobacterial 65 kDa antigen-specific immune responses in Chinese RA patients.
Adult↗
Abnormal splenic and thymic IL-4 and TNF-alpha expression in MRL-lpr/lpr mice.
The MRL-lpr/lpr and MRL-(++) mice were studied for the expression of cytokines in the spleen, lymph node, thymus, kidney and brain through the reverse transcription-polymerase chain reaction (RT-PCR). The frequencies of IL-4 and TNF-alpha expression in the thymus and spleen were significantly higher in MRL-lpr/lpr mice than in MRL-(++) mice from the age of 17 to 32 weeks. More importantly, IL-4 transcript was demonstrated in the early rather than in the terminal stage of the lupus disease. At the 20th week, MRL-lpr/lpr mice with active disease exhibited higher concentrations of IL-1 alpha, IL-6 and TNF-alpha in serum than MRL-(++) mice. Interestingly, in MRL-lpr/lpr but not MRL-(++) mice, the IL-6 concentration in cultured supernatants of the thymic cells was significantly higher than that of the splenic or lymph node cells. On the other hand, IL-6 and IL-1 beta were expressed in the brain and kidney of MRL-lpr/lpr mice but not of MRL-(++) mice. Cultured MRL-lpr/lpr mesangial cells could also express IL-6 but to a lesser extent. These results suggest that the abnormal splenic and thymic IL-4 and TNF-alpha expression may predispose the development of autoimmune reactions. The expression of IL-1 beta and IL-6 in the brain and kidney may be implicated in the damage of these two organs in MRL-lpr/lpr mice.
Animals↗
Antibody to Mycobacterium tuberculosis 65 kDa heat shock protein in patients with rheumatoid arthritis--a survey of antigen-specific antibody isotypes and subclasses in an endemic area of previous tuberculosis infection.
OBJECTIVE: To clarify the significance of the humoral immune response triggered by the Mycobacterium tuberculosis (M.tb) 65 kDa heat shock protein (hsp) in the pathogenesis of rheumatoid arthritis (RA). METHODS: M.tb 65 kDa hsp-specific IgG, IgA, IgM, and IgG subclass antibodies in serum or synovial fluid (SF) of RA and other disease patients were determined by enzyme linked immunosorbent assay (ELISA). RESULTS: RA patients did not show any characteristic increase in mycobacterial 65 kDa hsp-specific antibodies compared with healthy individuals. In contrast, antigen-specific IgG and IgG2 antibody titres in the serum of RA patients were significantly lower than those of patients with tuberculosis and normal controls. In addition, there was also no significant difference in antibody titre between the serum and SF of RA patients, nor was any significant difference found between the SF of RA and Reiter's patients. CONCLUSION: The failure to detect a significant increase in IgG anti-M.tb 65 kDa hsp antibodies in RA patients does not exclude the possibility of microbial immunity in the aetiology of RA. Nevertheless, anti-M.tb 65 kDa hsp antibodies clearly do not appear to be the disease specific markers for RA and their relatively reduced concentrations may argue against their playing a major role in the disease pathogenesis.
Antibodies, Bacterial↗
The physiologic and pathologic roles of Tamm-Horsfall glycoprotein in urinary system.
Tamm-Horsfall glycoprotein (THG), a unique renal glycoprotein, is synthesized exclusively by the epithelial cells of the thick ascending loop of Henle and early segment of distal convoluted tubules. The protein is the primary constituent of urinary hyaline cast. The aggregation and gel formation of THG in response to increasing concentrations of electrolytes and low pH within physiologic ranges may affect the permeability of water in this segment. The dual effect of THG on mononuclear cells renders the molecule to become a potent immunomodulator. The cytokine-binding activity of THG lets the kidney an important tissue for cytokine catabolism. The aggregation characteristics of THG also plays a role in pathologic states and leads to the persistence of interstitial deposits in several tubulointerstitial diseases. The induction of immune responses to this protein, including urinary tract infection, reflux nephropathy chronic active hepatic damage, elicites immune complex tubulointerstitial nephritis. It is expected that the detection of THG or its antibodies may aid in the diagnosis of renal tubular disorders.
Adjuvants, Immunologic↗