Biomedical subjects

Y Ohmoto

Publications and source records attributed to Y Ohmoto.

At least 19 recordsLinked to original sources

PubMed1999

Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.

We isolated the human adipose-specific and most abundant gene transcript, apM1 (Maeda, K., et al., Biochem. Biophys. Res. Commun. 221, 286-289, 1996). The apM1 gene product was a kind of soluble matrix protein, which we named adiponectin. To quantitate the plasma adiponectin concentration, we have produced monoclonal and polyclonal antibodies for human adiponectin and developed an enzyme-linked immunosorbent assay (ELISA) system. Adiponectin was abundantly present in the plasma of healthy volunteers in the range from 1.9 to 17.0 mg/ml. Plasma concentrations of adiponectin in obese subjects were significantly lower than those in non-obese subjects, although adiponectin is secreted only from adipose tissue. The ELISA system developed in this study will be useful for elucidating the physiological and pathophysiological role of adiponectin in humans.

Adiponectin↗

PubMed1999

Presence and potent immunosuppressive role of interleukin-10 in malignant pleural effusion due to lung cancer.

The presence and possible role of interleukin (IL)-10 were examined in malignant pleural effusion due to lung cancer. In 37 out of 55 cases examined, IL-10 was detectable in pleural effusion and the mean level with standard error was 62.1+/-12.1 pg/ ml. Spontaneous and lipopolysaccharide-induced production of anti-tumor cytokines such as IL-1beta and tumor necrosis factor (TNF)-alpha, by pleural macrophages, obtained from five patients with malignant pleurisy, were suppressed by IL-10. These findings suggest that IL-10 is present in the tumor-growing site and acts as a suppressive factor of local anti-tumor immunity in humans.

Aged↗

PubMed1999

Serum levels of soluble interferon Alfa/Beta receptor as an inhibitory factor of interferon in the patients with chronic hepatitis C.

Human serum contains a soluble form of interferon alfa/beta (sIFN alpha/beta) receptors, the functional and clinical significance of which has not been investigated in patients with chronic hepatitis C. In the present study, serum levels of sIFN alpha/beta receptor were assessed in 81 patients with chronic hepatitis C and correlated with the effectiveness of IFN therapy in these patients. Serum levels of sIFN alpha/beta receptor were significantly higher in patients with chronic hepatitis C than in healthy control patients (P <.0001). In these patients, serum levels of sIFN alpha/beta receptor were correlated with those of alanine transaminase (ALT) (P <.05), (2'-5')serum oligo(A) synthetase (2-5AS) (P <.0001), and pathological stages of liver fibrosis (P <.01). In 55 patients with chronic hepatitis C who underwent IFN therapy, there was an inverse correlation between the pretherapeutic serum levels of sIFN alpha/beta receptor and the rate of increase in serum levels of 2-5AS after the start of IFN (P <.01). Pretherapeutic serum levels of sIFN alpha/beta receptor were significantly lower in patients who showed sustained response to IFN therapy compared with those who did not respond to the therapy (P <.05). Multivariate analysis showed that low levels of serum sIFN alpha/beta receptor (</=4.0 ng/mL) (P <.05) and serological hepatitis C virus genotype II (P <.05) were independent variables contributing to sustained response to IFN therapy. Thus, pretherapeutic serum levels of sIFN alpha/beta receptor were correlated with the effectiveness of IFN therapy, suggesting that sIFN alpha/beta receptor suppresses the effectiveness of IFN therapy in patients with chronic hepatitis C.

2',5'-Oligoadenylate Synthetase↗

PubMed1999

Comparison of suppressive effects of a new anti-inflammatory compound, FR167653, on production of PGE2 and inflammatory cytokines, human monocytes, and alveolar macrophages in response to endotoxin.

FR167653 [1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8 (4-pyridyl) pyrazoro [5-1-c] [1,2,4] triazin-2-yl]-2-phenylethanedion sulfate monohydrate] was developed to inhibit proinflammatory cytokine production. However, the effects of FR167653 on prostanoid production are unclear. We investigated the effect of FR167653 on proinflammatory cytokine and prostaglandin (PG) production by lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes and alveolar macrophages (AM) from the same individuals, and compared the effects in monocytes and AM. FR167653 inhibited interleukin-1beta and tumor necrosis factor alpha production. The effect on PGE2 production was assessed by four parameters. FR167653 inhibited PGE2 synthesis and LPS induction of cyclooxygenase activity. Western and Northern blot analyses revealed that LPS induction of cyclooxygenase-2 expression was attenuated by this compound. The suppression in monocytes was greater than that in AM. We concluded that the reduction of LPS-induced PGE2 synthesis by FR167653 was due to inhibition of cyclooxygenase-2 production. These results show that FR167653 may be therapeutically useful for inhibiting production of both inflammatory cytokines and PG production in inflammatory diseases.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Vascular endothelial growth factor in malignant pleural effusion associated with lung cancer.

The presence of vascular endothelial growth factor (VEGF) was examined by enzyme immunoassay in 60 cytology-documented malignant pleural effusions associated with primary lung cancer and 51 other benign and malignant pleural effusions. Exudative pleural effusions contained significantly higher amounts of VEGF than transudative pleural effusions. Among exudative pleural effusions, levels of VEGF in malignant pleural effusions associated with lung cancer were significantly higher than those of benign exudative pleural effusions. There was no significant difference in pleural VEGF in patients with different histological types or clinical stages of lung cancer. Serial measurement of pleural VEGF levels was performed in six lung cancer patients treated with intrapleural instillation of recombinant interferon gamma, and reduction of pleural effusion was associated with decreasing pleural VEGF levels. These findings suggest that VEGF has a role in the accumulation of exudative pleural effusions, especially that of malignant pleural effusion associated with lung cancer.

Adenocarcinoma↗

PubMed1999

Expression of transforming growth factor (TGF)-alpha, TGF-beta(2) and interleukin 8 messenger RNA in postsurgical and cultured lens epithelial cells obtained from patients with senile cataracts.

BACKGROUND: Testing our hypothesis that residual lens epithelial cells (LEC) participate in the pseudophakic inflammation by producing cytokines, prostaglandins (PG) or both, we detected interleukin-1 (IL-1), IL-6, b-FGF and PGE(2) in the incubation medium of cultured LEC. This paper describes our subsequent work on the expression of TGF-alpha, TGF-beta(2), IL-4 and IL-8 mRNA in postsurgical and cultured LEC. METHODS: The anterior lens capsule with attached LEC was obtained by anterior capsulotomy during cataract surgery and cultured. Specimens in serum-free medium immediately after surgery or those in serum-added medium after 2 weeks of culture were used. Reverse transcriptase-polymerase chain reaction (PCR) and electrophoresis were used to detect mRNA coding for TGF-alpha, TGF-beta(2), IL-4 and IL-8 in human cataract LEC. RESULTS: Electrophoresis of the PCR products showed that appropriately sized amplification products were specific for TGF-alpha and TGF-beta(2) in the specimens immediately after surgery and after culturing, and IL-8 in the cultured LEC. IL-4 was not detected in either group of specimens. CONCLUSIONS: Human cataract LEC synthesize TGF-alpha and TGF-beta(2) mRNA in situ and after culturing, and the cultured LEC also synthesize IL-8 mRNA. These cytokines may be synthesized by LEC in vitro and play an important role in an autocrine or paracrine manner in the proliferative process of LEC after cataract surgery, which can cause inflammation and aftercataract.

Aged↗

PubMed1999

Identification of the human sperm protein that interacts with sperm-immobilizing antibodies in the sera of infertile women.

OBJECTIVE: To identify the target antigen of sperm-immobilizing antibodies present in the circulation of infertile women. DESIGN: Laboratory research. SETTING: Academic research laboratory. PATIENT(S): Twenty-nine infertile women with sperm-immobilizing antibodies, 22 infertile women with other disorders, and 20 fertile women. INTERVENTION(S): Titers of antibodies to the sperm protein, rSMP-B, were determined by ELISA using as substrate the synthetic peptide segment (rSMP-230) that corresponds with the hydrophilic domain of rSMP-B. Tests for sperm immobilization and zona pellucida penetration were performed using the human IVF system. MAIN OUTCOME MEASURE(S): Human sera with sperm-immobilizing activity were assayed for the presence of antibodies to rSMP-230. Polyclonal antibodies to rSMP-230 were assessed for the same biologic activities as sperm-immobilizing antibodies. RESULT(S): Antibodies to rSMP-230 were detected in 10 (34%) of 29 sera obtained from women with immunologic infertility. In contrast, only one serum sample (2%) from women without sperm-immobilizing activity had a low titer of antibodies to rSMP-230. Polyclonal antibodies to rSMP-230 completely immobilized human sperm in the presence of complement and blocked sperm penetration across the zona pellucida. CONCLUSION(S): The human sperm protein, rSMP-B, probably is the target antigen of sperm-immobilizing antibodies.

Adult↗

PubMed1999

Production of interleukin-10 by alveolar macrophages from lung cancer patients.

Interleukin (IL)-10 is known to be an autoregulatory factor of functions of monocyte macrophages. The purpose of this study was to determine whether IL-10 production by alveolar macrophages (AMs) is altered in patients with lung cancer. AMs were obtained by bronchoalveolar lavage from 25 patients with lung cancer and 14 control patients. The production of IL-10 by AMs was quantitated by enzyme immunoassay with or without stimulation with lipopolysaccharide (LPS). No significant difference in spontaneous and LPS-stimulated IL-10 production by AMs was observed between lung cancer patients and control patients (mean +/- SEM; 288.0 +/- 56.7 vs. 249.6 +/- 58.4 pg ml-1). IL-10 production of LPS-stimulated AMs was not impaired even in lung cancer patients with systemic metastasis. IL-4 failed to suppress LPS-induced production of IL-10 by AMs both in control patients and in lung cancer patients. In eight patients with lung cancer, IL-10 production by AMs was estimated before and after systemic chemotherapy and IL-10 production by LPS-stimulated AMs tended to increase after systemic chemotherapy from 152.3 +/- 51.9 to 278.0 +/- 112.8 pg ml-1. As IL-10 is a potent inhibitor of tumour angiogenesis, an important process of tumour progression, these results suggest that, even in advanced cancer patients, macrophages can produce potent angiogenesis inhibitor and systemic chemotherapy may augment this inhibitory activity in the lung.

Adult↗

PubMed1999

Variation in the immune response to adenoviral vectors in the brain: influence of mouse strain, environmental conditions and priming.

E1-deleted adenoviral vectors expressing the bacterial beta-galactosidase gene were inoculated into the brain of unprimed and primed C3H.He or C57BL/6J mice housed under either conventional or specific-pathogen-free (SPF) conditions. The kinetics of immune responses to both the vector and the transgene were investigated. In mice previously sensitized to adenovirus, the leukocyte infiltrate in the brain was dominated by CD8+ T cells, whereas in unprimed mice CD4+ T cells were present at higher levels. As expected, antibody titres to both adenovirus and beta-galactosidase were higher in primed mice than in unprimed mice after intracranial inoculation. C3H.He mice consistently made higher antibody responses than C57BL/6J mice. Although adenoviral vectors induced an inflammatory response under all conditions, mice housed in SPF facilities exhibited less inflammation than conventional mice and transgene expression persisted for longer. Irrespective of whether the mice had been deliberately primed to adenovirus, antibody titres were consistently lower in SPF mice compared with conventional mice. This study clearly demonstrates that environmental conditions, as well as previous priming to adenovirus, will affect both the quality and duration of the immune response triggered by gene delivery to the brain.

Adenoviridae↗

PubMed1999

An assessment of the immunological environment based on intratumoral cytokine production in renal cell carcinoma.

OBJECTIVE: To assess the immunological relationship between tumour and host, focusing on the production of T-cell helper (Th) subset-derived cytokines in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised 35 patients (19 men and 16 women, mean age 56.9 years, range 39-78) with RCC, who had undergone nephrectomy. Using enzyme-linked immunosorbent assays, the levels of Th1-derived cytokines were measured, including interleukin (IL)-2 and interferon (IFN)-gamma, and Th2-derived cytokines, including IL-4, IL-5, IL-6, IL-10 and others. RESULTS: There was no detectable IL-2 or IFN-gamma production (below the detection limit) except in two patients; IL-4 was produced in 18 patients (51%) and of these, 15 (43%) showed a higher level than the mean. IL-5 was produced in 12 patients (34%), all of whom showed a higher level than the mean, and IL-6 was produced in 32 (91%) of whom 10 (29%) showed a higher level than the mean. IL-10 was detected in 28 patients (80%) of whom 14 (40%) showed a higher level than the mean. The production of these cytokines was closely related to the stage and grade of malignancy. Furthermore, there were significant correlations between the levels of production of IL-4 and IL-5 (r2=0.92), IL-4 and IL-10 (r2=0.91), and IL-5 and IL-10 (r2=0.85). CONCLUSION: The intratumoral immunological environment in patients with RCC shows a tendency to produce Th2-related cytokines in accordance with the stage and grade; this suggests a role in humoral but not in cellular immunity.

Adult↗

PubMed1999

Possible involvement of interleukin-1 in cyclooxygenase-2 induction after spinal cord injury in rats.

A standardized compression injury of rat spinal cord brought about a time-dependent biphasic production of thromboxane A2 (detected as thromboxane B2) and prostaglandin I2 (detected as 6-ketoprostaglandin F1alpha). Thromboxane B2 was predominant during the first 1 h, whereas the 6-ketoprostaglandin F1alpha level exceeded that of thromboxane B2 at 8 h postinjury. As examined by inhibitor experiments and northern blotting, cyclooxygenase-1 was responsible for the first phase, and cyclooxygenase-2 was involved in the second phase. On compression injury the levels of interleukin-1alpha and -1beta detected as mRNA and protein increased and peaked at 2-4 h. Injection of exogenous interleukin-1alpha into the spinal cord resulted in an increase of cyclooxygenase-2 mRNA content and a predominant production of 6-ketoprostaglandin F1alpha resembling the second phase of eicosanoid production. Concomitantly, extravascular migration of polymorphonuclear leukocytes was enhanced after the interleukin-1alpha injection. These cells together with vascular endothelial cells and glial cells were stained positively with an anti-cyclooxygenase-2 antibody. The results suggest that the immediate eicosanoid synthesis after spinal cord injury was due to the constitutive cyclooxygenase-1 and the delayed synthesis of eicosanoids was attributable to the induction of cyclooxygenase-2 mediated by interleukin-1alpha.

Animals↗

PubMed1999

MIP-1alpha and MCP-1 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis.

BACKGROUND: The precise molecular mechanisms of macrophage (Mphi) recruitment and activation in crescentic glomerulonephritis remain to be investigated. We hypothesized that locally produced macrophage inflammatory protein (MIP)-1alpha and monocyte chemoattractant protein (MCP)-1 via the chemokine receptors participate in the pathophysiology of human crescentic glomerulonephritis by recruiting and activating Mphi. METHODS: We investigated the levels of MIP-1alpha and MCP-1 by enzyme-linked immunosorbent assay (ELISA) in 20 healthy subjects, 20 patients with crescentic glomerulonephritis, and 41 control patients with various other renal diseases. The presence of MIP-1alpha, MCP-1, and the cognate chemokine receptor for MIP-1alpha, CCR5, in the diseased kidneys was evaluated by immunohistochemical and in situ hybridization analyses. RESULTS: MIP-1alpha-positive cells were mainly detected in crescentic lesions, whereas MCP-1 was mainly in the interstitium. In addition, we detected CCR5-positive cells in diseased glomeruli and interstitium. Urinary MIP-1alpha was detected in crescentic glomerulonephritis, even though it was below detectable levels in healthy subjects and in patients with other renal diseases without crescents. Urinary MIP-1alpha levels in the patients with crescentic glomerulonephritis were well correlated with the percentage of cellular crescents and the number of CD68-positive infiltrating cells and CCR5-positive cells in the glomeruli. However, urinary MCP-1 levels were well correlated with the percentage of both total crescents and fibrocellular/fibrous crescents and the number of CD68-positive infiltrating cells in the interstitium. Moreover, elevated urinary levels of both MIP-1alpha and MCP-1 dramatically decreased during glucocorticoid therapy-induced convalescence. CONCLUSIONS: These observations suggest that locally produced MIP-1alpha may be involved in the development of cellular crescents in the acute phase via CCR5 and that MCP-1 may be involved mainly in the development of interstitial lesions in the chronic phase when fibrocellular/fibrous crescents are present, possibly through Mphi recruitment and activation.

Adolescent↗

PubMed1999

Increased urinary excretion of macrophage-colony-stimulating factor (M-CSF) in patients with IgA nephropathy: tonsil stimulation enhances urinary M-CSF excretion.

Upper respiratory tract infection including chronic tonsillitis is considered to be involved in the onset and/or the progression of IgA nephropathy. It is well known that deterioration of urinary findings occurs after episodes of upper respiratory tract infection in patients with IgA nephropathy. We previously showed that the expression of macrophage-colony-stimulating factor (M-CSF) is increased in the glomeruli of patients with IgA nephropathy and correlated with glomerular mesangial proliferation, suggesting that M-CSF plays an important role in the progression of IgA nephropathy. In the present study, we measured the serum and urinary concentrations of M-CSF in patients with IgA nephropathy associated with chronic tonsillitis. Furthermore, we evaluated the effects of the local provocation test of tonsils (mechanical tonsil stimulation) on the serum and urinary concentrations of M-CSF in the following three groups: (1) IgA nephropathy with severe mesangial proliferation, (2) IgA nephropathy with mild mesangial proliferation, and (3) patients with chronic tonsillitis without renal disease. The serum and urinary levels of M-CSF in the groups with severe and mild IgA nephropathy were significantly higher than those in the chronic tonsillitis group. The urinary M-CSF level but not the serum M-CSF level was positively correlated with the degrees of mesangial proliferation and glomerular M-CSF expression in the renal biopsy specimens. The urinary M-CSF concentration was significantly increased after tonsillitis stimulation in both mild and severe IgA nephropathy groups. Enhanced urinary excretion of M-CSF prolonged for 7 days after tonsil stimulation in the severe IgA nephropathy group; in contrast, the urinay M-CSF level was increased for only 2 days after tonsil stimulation in the mild IgA nephropathy group. The urinary M-CSF level was not changed in the chronic tonsillitis group after tonsil stimulation. The serum concentrations of M-CSF were not changed after tonsil stimulation in these three groups. Our present results suggest that tonsil stimulation contributes to the progression of IgA nephropathy via enhancement of glomerular production of M-CSF. The urinary excretion of M-CSF may be a useful predictor to evaluate the relevance of chronic tonsillitis to the disease and the indication of tonsillectomy in patients with IgA nephropathy.

Adult↗

PubMed1999

Expression of cytokine and adhesion molecule mRNA in atherectomy specimens from patients with coronary artery disease.

Coronary arteriosclerosis is an underlying condition in acute myocardial infarction (AMI), unstable angina pectoris (UAP) and stable angina pectoris (SAP), and is also related to restenosis (RS) following coronary intervention. To investigate the pathogenesis of this condition, a quantitative reverse transcriptase polymerase chain reaction was used to determine relative levels of mRNA for interleukin (IL)-1beta, IL-6, IL-8, transforming growth factor beta (TGF-beta), intercellular adhesion molecule (ICAM)-1, E-selectin and vascular cell adhesion molecule (VCAM)-1 using directional coronary atherectomy (DCA) specimens. Eleven patients with AMI, 7 with UAP, 10 with SAP and 6 with RS following a previous coronary intervention underwent DCA. The mRNA intensity for each molecule was expressed by comparing it with that of beta-actin mRNA. The AMI and UAP patients showed high frequencies of mRNA for IL-1beta, IL-8, TGF-beta, and ICAM-1 together with strong intensities of expression, whereas SAP patients showed decreased mRNA expression for these molecules. Increased IL-6 mRNA expression was observed only in AMI samples. Specimens from RS patients revealed an accumulated expression of proinflammatory cytokines, except for IL-6, as well as of TGF-beta. The study suggests that variation in mRNA expression may reflect the pathophysiology of specific types of coronary artery disease, and remodeling following vascular injury.

Aged↗

PubMed1998

Effects of cilostazol on late lumen loss after Palmaz-Schatz stent implantation.

Cilostazol inhibits intimal hyperplasia after stent implantation into canine iliac arteries. To determine the antiproliferative effect of this agent, cilostazol or aspirin was randomly given for 6 mo to 36 patients treated with Palmaz-Schatz stent implantation. Initial success was obtained in 34 patients. Repeat angiography was performed in 33 patients, and the complete angiographic data were obtained in 22 lesions of the cilostazol group and in 21 lesions of the aspirin group. The reference diameter and minimal luminal diameter were similar in both groups before and immediately after stent implantation. At follow-up, minimal luminal diameters were significantly greater in the cilostazol group than in the aspirin group (P < 0.001). Late loss and loss index were significantly smaller in the cilostazol group than in the aspirin group (P < 0.001). These results suggest that cilostazol reduces angiographic late lumen loss and thereby may reduce the incidence of restenosis after Palmaz-Schatz stent implantation.

Aged↗

PubMed1998

Expression of interleukin-12 in synovial tissue from patients with rheumatoid arthritis.

OBJECTIVE: To examine the importance of interleukin-12 (IL-12) as a factor in the interferon-gamma (IFNgamma)-dominant T cell cytokine response in the synovial tissue of patients with rheumatoid arthritis (RA). METHODS: The expression of IL-12 in synovial tissue samples from patients with chronic RA (> or = 2 years) was compared with that in samples from osteoarthritis (OA) patients by detection of IL-12 p40 messenger RNA (mRNA) using reverse transcriptase-polymerase chain reaction, measurement of IL-12 p70 protein in culture supernatants of tissue cells by immunoassay, and immunostaining of tissue sections with anti-IL-12 p70. The production of IFNgamma by RA synovial tissue cells cultured with or without IL-12 was determined. In addition, T cells were obtained 14 days after culturing RA synovial tissue cells with IL-2 alone or with IL-2 plus IL-12, neutralizing anti-IL-12, or IL-4, and cytokine patterns (i.e., IFNgamma and IL-4 levels) were determined by stimulating cells for 24 hours with anti-CD3 plus phorbol myristate acetate. RESULTS: Synovial tissues from RA patients more strongly expressed IL-12 p40 mRNA than did OA tissues. Dissociated tissue cells from 21 of 37 RA patients spontaneously released detectable amounts of IL-12 p70 (> or = 12.5 pg/ml) in culture, whereas production of IL-12 by OA tissues was limited. By immunohistochemical analysis, IL-12-producing cells were localized mainly in the sublining layer of RA synovium, and mostly expressed the CD68 antigen. Levels of IFNgamma production by RA synovial tissue cells were potently and selectively enhanced by IL-12. The ability of IL-2-expanding synovial T cells to produce IFNgamma was augmented by costimulation with IL-12 and diminished by anti-IL-12, while it was not affected by IL-4. CONCLUSION: These data suggest that IL-12, produced mainly by macrophage-lineage cells, may be involved in IFNgamma-dominant cytokine production by infiltrating T cells in joints with chronic RA.

Arthritis, Rheumatoid↗

PubMed1998

Up-regulation of vascular endothelial growth factor in response to glucose deprivation.

Vascular endothelial growth factor (VEGF), also known as a vascular permeability factor (VPF), is an endothelial specific mitogen and is a potent inducer of angiogenesis. Recently it has been reported that hypoxia induces VEGF mRNA expression in various cells. Since both oxygen and glucose are required for efficient production of energy, we examined the effect of glucose deprivation on VEGF mRNA expression and VEGF protein production in U-937 (a human monocytic cell line) cells. Both the mRNA expression and secretion of VEGF increased after exposure to low glucose. Addition of L-glucose, the L-stereoisomer of D-glucose, did not prevent the up-regulation of VEGF expression. The conditioned medium from glucose-deprived cells, followed by supplementation with glucose, did not up-regulate VEGF mRNA expression in U-937 cells. The low glucose-induced VEGF mRNA expression returned to the control level after supplementation with D-glucose. Furthermore, oligomycin, a mitochondrial ATP synthase inhibitor, increased VEGF protein production. The results suggest that the up-regulation of VEGF mRNA in U-937 cells in response to glucose deprivation is not mediated by autocrine factors from the cells nor is the osmotic change of the medium mediated by the deficiency of glucose metabolism in the cells. Our results also suggest that the intracellular ATP depletion due to glucose deprivation may be one of the causes for increased VEGF mRNA expression. We speculate that local hypoglycemia may act as an essential trigger for angiogenesis through the VEGF gene expression.

Adenosine Triphosphate↗

PubMed1998

Endogenous neutralizing anti-IL-1 alpha autoantibodies in inflammatory skin diseases: possible natural inhibitor for over expressed epidermal IL-1.

Interleukin 1alpha (IL-1alpha) is thought to play a central role in inflammatory reactions of the skin. Its excessive production and discharge by keratinocytes has been implicated in psoriasis, bullous diseases and other skin diseases. In addition to the type 2 IL-1 receptor and the IL-1 receptor antagonist, anti-IL-1 antibody in human serum has been proposed as a potential means to down regulate systemic responses attributable to IL-1. However, the relationship of these antibodies to disease and particularly to disease pathogenesis is still unclear. To understand this relationship, we characterized the anti-IL-1 autoantibody in sera from various skin diseases. IL-1alpha and IL-1beta radioimmunoassay, and immuno-blotting study showed the existence of IL-1alpha autoantibody but not autoantibodies to IL-1beta or pro-IL-1beta. High titer of anti-IL-1alpha autoantibodies were detected in the sera from inflammatory skin diseases with epidermal injury, including psoriasis, palmoplantar pustulosis, pustular psoriasis, pemphigus and lichen planus. In contrast, few samples from non-epidermodestructive bullous pemphigoid, atopic dermatitis and healthy normal controls had autoantibodies. The titer of anti-IL-1alpha autoantibodies showed some relation to the clinical course of psoriasis and pemphigus. Anti-IL-1 autoantibody neutralized rhIL-1alpha in D10.G4 assay and inhibited receptor binding of FITC-rhIL-1alpha. Taken together present data, the keratinocyte derived IL-1alpha could be a source of autoantigen that provokes production of endogenous anti-IL-1alpha autoantibody, which may regulate IL-1alpha mediated cutaneous inflammation.

Adult↗