Amounts Of IL-1β Research Articles

S1791 R-Type Calcium Channels Mediate Inhibitory Neuromuscular Transmission and Impair Peristalsis In Vitro in the Guinea-Pig Ileum

BACKGROUND/AIM: Enterochromaffin (EC) cells are the best characterized subset of enteric endocrine cells and are the main source of 5-hydroxytryptamine (5-HT) in the gut. Previously we have shown an important immuno-endocrine axis in the gut, where CD4+ T cells play a key role in generation of EC cell hyperplasia and in up-regulation of 5-HT production in infection-induced gut inflammation (Gut 2007; 56: 949). However, the role of EC cells/5HT in regulation of inflammation or in host defense in enteric infection remains to be determined. The aim of this study was to investigate the role of 5-HT in the development of infection-induced gut inflammation and in host defense in a model of enteric infection. METHODS: Tryptophan hydroxylase1-deficient mice (TPH1-/-) which lack 5-HT in gut and wild type (TPH1+/+) mice were infected with nematode, Trichuris muris and sacrificed on various days post-infection (pi) to study the worm expulsion, macrophage infiltration by immunohistochemistry, myeloperoxidase (MPO) activity, and cytokines (IL-β,IL-4 and IL13) in colon by ELISA. Role of 5-HT in production of pro-inflammatory mediators was further studied by culturing macrophages harvested from peritoneal cavity of naive TPH1+/ + mice with 5-HT, and assessing IL-1β production after LPS stimulation. RESULTS: Worm expulsion from the intestine was significantly delayed in TPH1-/mice as compared to TPH1+/+ mice in T. muris infection (worm numbers: 24.2±3.8 vs. 40±6.7 in TPH1+/+ vs. TPH1-/mice on day 21 pi; p<0.05). There was significant down-regulation of infiltration of F4/80 positive macrophages in the colon of TPH1-/mice compared to TPH1+/+ mice after infection. We also observed significantly lower MPO activity and IL-1β levels in colon of TPH1-/-mice as compared to TPH1+/+ mice after infection (MPO activity and IL-1β levels were 41.8±5.3 u/mg and 81.3±4.5 pg/mg protein vs. 26.7±4.8 u/mg and 57±3.9 pg/mg protein in TPH1+/+ vs. TPH1-/mice on day 21 pi; p<0.05). There was no significant difference in IL-4 and IL-13 levels in colon between TPH1-/and TPH1+/+ after infection. We also observed higher amount of IL-1β in the culture supernatant of macrophages harvested from TPH1+/+ mice after stimulation with 5-HT. CONCLUSION: These results provide evidence for an important role for EC cells/5-HT in host defense and in generation of gut inflammation in enteric infection. Considering the strategic location of EC cells in gut mucosa and the importance of 5-HT in intestinal homeostasis, these results provide new insights into the mechanisms of gut pathology and host defense which may ultimately lead to improved therapeutic strategies in various gut disorders.

Modulation of monocyte hyperresponsiveness to TLR ligands by 1,25-dihydroxy-vitamin D3 from LADA and T2DM

To investigate the differences of Toll-like receptors (TLRs) expression and response of monocyte and modulation of 1,25-dihydroxy-vitamin D3 on monocyte activity. Peripheral blood monocytes were collected from 23 healthy controls, 18 latent autoimmune diabetes in adults (LADA), and 22 type 2 diabetes mellitus (T2DM), respectively. CD14, TLR2 and TLR4 expression were analyzed. Moreover, the effect of 1,25-dihydroxy-vitamin D3 (1,25(OH) 2D3) on monocyte response to lipoteichoic acid (LTA) and lipopolysaccharide (LPS) was evaluated in vitro by measuring phosphorylation level of NF-κB-p65 and associated cytokine production. Monocytes showed significantly higher surface CD14 expression from LADA compared with that from T2DM and controls, and high expression of TLR4 from LADA and T2DM than controls. After incubation with LPS or LTA, decreased surface expressions of CD14 were observed on monocytes from T2DM and controls, in contrast to the increased on monocytes from LADA. Activation of NF-κB and amounts of IL-1β and TNF-α production by stimulation with ligands significantly increased in LADA and T2DM, which was modulated by 1,25(OH) 2D3 to similar level, as compared to controls. The modulation of 1,25(OH) 2D3 on monocytes makes us to consider more potency of vitamin D3 as therapy in LADA and T2DM.

Decreased Interleukin‐1β and Elastase in the Gingival Crevicular Fluid of Individuals Undergoing Anti‐Inflammatory Treatment for Rheumatoid Arthritis

The primary aim of this study was to compare the inflammatory activity in the gingival crevicular fluid (GCF) in a group of patients with rheumatoid arthritis (RA) and a group of matched controls. Secondarily, we aimed to evaluate the effect of rheumatologic treatment on periodontal inflammation. Seventeen individuals with RA with a mean duration of disease of 12.1 (± 9.9) years and the same number of systemically healthy individuals matched for age, gender, periodontal status, and tobacco use were selected. Medication data were registered, and GCF was collected by means of an intracrevicular washing method. Besides clinical registrations, periodontal inflammation was assessed by analysis of the cytokines interleukin (IL)-1β and -18 and of elastase activity. Amounts of IL-1β and total elastase were significantly lower in the patient group. IL-1β and total elastase had a significant and strong correlation in the RA group (rs = 0.883). This correlation was not observed in the control group. The anti-inflammatory treatment taken by RA patients might influence the periodontal inflammation status represented by IL-1β and elastase in the GCF.

Activation of synovial fibroblasts by laminin-1 and transforming growth factor beta induces expression of stromelysins independently of TNFα, IL-1β or NF-κB

Recently it was shown that attachment of synovial fibroblasts (SF) from rheumatoid arthritis patients to laminin-111 (LM-111) induced an elevated expression of stromelysin-1 (MMP-3). We therefore investigated the regulation of additional matrix metalloproteinases (MMPs) and their specific tissue inhibitors of matrix metalloproteinases (TIMPs) by attachment to LM-111 in the presence of transforming growth factor beta (TGFβ). Changes in steady-state mRNA levels encoding TIMPs and MMPs were investigated by quantitative RT-PCR. Production of MMPs and cytokines was monitored by a multiplexed immunoarray or by ELISA. Signal transduction pathways were studied by immunoblotting. Attachment of SF to LM-111 in the presence of TGFβ induced significant increases in stromelysin-1 mRNA (12.35-fold, P < 0.001) and protein (mean 62 ng/ml, sixfold, P < 0.008). Expression of stromelysin-2 (MMP-10) mRNA (11.68-fold, P < 0.05) and protein (54 ng/ml, 20-fold, P ≥ 0.02) was significantly activated as well. All other TIMPs and MMPs investigated failed to show this LM-111-facilitated TGFβ response. Induction of stromelysin-1 and stromelysin-2 was associated with the activation of transcription factors c-fos and Egr-1, but phosphorylation of NF-κB was not observed. Further, LM-111-activated and TGFβ-activated SF failed to produce remarkable amounts of IL-1β or TNFα. We conclude that costimulation of synovial fibroblasts by LM-111 together with TGFβ suffices to induce significant expression of MMP-3 and MMP-10 by SF and that this induction is independent of phosphorylation of NF-κB.

Amount of seminal IL-1β positively correlates to HIV-1 load in the semen of infected patients

Background Cytokines present in the sperm could influence the heterosexual transmission of HIV by modulating viral titers and influencing the early immune response in the vaginal mucosa. Objectives To assess the relation between cytokine concentrations and HIV status in the seminal plasma. Study design Twenty-five HIV positive subjects were tested for cytokine content and HIV-1 load in seminal and blood plasma through a cross-sectional study. Results HIV positive subjects exhibited a significantly higher amount of seminal IL-1β as compared to a group of 33 HIV negative controls. In HIV positive subjects, amounts of IL-1β and HIV-1 RNA in semen were significantly correlated and a trend for correlation was found between seminal IL-1β and blood HIV-1 RNA. Amount of seminal IL-1β was significantly lower in patients under HAART, according to the decrease of their viral loads in blood and semen. Conclusions Considering that IL-1β is known to enhance viral replication and to promote immune response, its dosage in semen could represent an interesting marker for identifying patients at high risk for HIV heterosexual transmission.

Suppression of interleukin-10 release from human periodontal ligament cells by interleukin-1β in vitro

Periodontitis is characterized by an inflammatory process induced by periodontopathogenic bacteria in the subgingival plaque. Periodontal inflammation can be enhanced by both an increase of inflammatory stimulators, e.g. interleukin (IL)-6, and a decrease of inflammatory inhibitors, e.g. IL-10. The amount of IL-1β is known to be increased in gingival tissues and in the gingival crevicular fluid from inflamed sites compared to healthy sites. This in vitro study sought to clarify whether IL-1β (1 ng/ml) has a regulatory effect on the release of these two cytokines from human periodontal ligament (PDL) cells. PDL cells derived from healthy premolars were grown in the presence and absence (control) of IL-1β. The concentration of IL-6 and IL-10 in the supernatants was assessed by enzyme-linked immunosorbent assay after 48 h of culture. PDL cells incubated with IL-1β released significantly ( p<0.05) higher amounts of IL-6 and significantly ( p<0.01) smaller amounts of IL-10 compared to control. These results give further support to the observation that IL-1β can increase the IL-6 secretion from PDL cells. Moreover, they provide original evidence that PDL cells secrete IL-10, which can be suppressed by IL-1β. It is concluded that PDL cells can function as accessory immunoinflammatory cells amplifying the inflammatory process in periodontitis and, thereby, contributing to periodontal breakdown.

Interleukin 1 and interleukin 1β converting enzyme (caspase 1) expression in the human colonic epithelial barrier. Caspase 1 downregulation in colon cancer

BACKGROUNDInterleukin (IL) 1β converting enzyme (now known as caspase 1) is able to process pro-IL-1β into its active form and is involved in proapoptotic signalling.AIMSTo characterise IL-1 and caspase 1...

Increased expression of interleukin-1 beta and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the hypertrophied and failing heart with pressure overload.

Studies on the effects of proinflammatory cytokines on the heart suggest that they play some roles in the pathogenesis of congestive heart failure (CHF). To determine the involvement of proinflammatory cytokine in cardiac hypertrophy and CHF induced by mechanical overload, we investigated the expression of interleukin (IL)-1 beta and monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein-1 (MCP-1) in the left ventricle (LV) of Dahl salt-sensitive (DS) rats that showed hypertrophy of the LV induced by hypertension and subsequently developed CHF. The IL-1 beta mRNA content in the LV of DS rats increased 3.9-fold when LV hypertrophy developed, and the increase reached 6.2-fold at the CHF stage compared with that of age-matched Dahl salt-resistant (DR) rats. The amount of IL-1 beta in the LV was positively correlated with the LV weight/body weight ratio. Most of the IL-1 beta immunoreactivity was localized in the endothelial cells and interstitial macrophages. The mRNA levels of MCAF in the LV increased 3.6-fold at 11 weeks and reached 4.8-fold at the CHF stage relative to the age-matched DR rats. MCAF protein was localized to the endothelial cells and interstitial macrophages. In DS rats, the number of interstitial macrophages increased diffusely throughout the LV. We suggest that increased chemokine expression, macrophage infiltration, and proinflammatory cytokine expression play some role in the pathogenesis of cardiac hypertrophy and failure induced by chronic mechanical overload.

Relationships between clinical parameters, interleukin 1B and histopathologic findings of gingival tissue in periodontitis patients

IL-1β is one of the cytokines which can induce bone resorption and connective tissue destruction. Previous studies demonstrated that the amount of IL-1β in gingival crevicular fluid (GCF) was closely related to the severity of gingival index (GI) and probing depth (PD). To further investigate whether the amount of IL-1β in GCF and the tissues adjacent to the periodontal pockets can reflect the degree of inflammation and destruction of these tissues, the GCF and inflamed gingival specimens were harvested from 14 periodontal patients and IL-1β in these samples was measured by ELISA. Clinical parameters of the sampled teeth were also recorded. Possible relations among periodontal parameters, GCF or tissue IL-1β and the degrees of inflammation in tissue sections were analysed statistically. The results showed that with increasing GI and PD, there was an elevation of GCF and tissue IL-1β activity. GCF flow also showed a tendency to increase with a higher percentage of inflammatory infiltrate. The GCF and tissue IL-1β activity were significantly correlated with clinical parameters (GI, PD and GCF flow), as well as with the percentage of inflammatory infiltrate and tissue alterations. With the exception of a significantly negative correlation with the extent of inflammation, no obvious relation between the GCF or tissue concentration of IL-1β and the state of tissue pathology could be detected. In conclusion, measurements of IL-1β activity in GCF or diseased tissues based on the classification of clinical parameters can reflect the degree of inflammation within periodontal disease tissue. These observations indicate that clinical parameters can provide reliable means for evaluation of the severity of periodontal disease, and that IL-1β plays a pivotal role in the pathogenic mechanism of periodontal tissue destruction.

Production of Interleukin-1 Receptor Antagonist and Interleukin-1β by Peripheral Blood Mononuclear Cells Is Differentially Regulated

AbstractWe studied the relationship between the production of the 23-Kd interleukin-1 receptor antagonist (IL-lra) and IL-1β in cultures of human peripheral blood mononuclear cells (PBMC) using a specific radioimmunoassay for IL-Ira that had a sensitivity of 166 ±11 pg/mL PBMC cultured without human serum made little IL-1ra or IL-1β. In the presence of 1% AB serum, there was no increase in IL-1 p (0.25 ± 0.13 ng/mL) but IL-1ra production increased sevenfold to 3.4 ± 0.5 ng/mL. IgG (2.5 to 100 μg/mL IgG) or granulocyte-macrophage colonystimulating factor (GM-CSF) (1 to 100 ng/mL) had no significant effect on IL-1β production but increased IL-Ira production up to 18-fold (18.2 ± 3.9 ng/mL). Using endotoxin as a stimulant, 82% ± 2% of IL-1 ra was secreted in comparison with 52% ± 9% of IL-1β. Culture conditions of PBMC influenced the production of IL-1ra but not IL-ip. Rocking endotoxin-stimulated PBMC produced 75% less IL-1ra but the same amount of IL-1β when compared with PBMC cultured in stationary plastic tubes. Rocking IgG-orGM-CSF-stimulated PBMC also produced 75% to 80% less IL-1ra. GM-CSF or IL-1β at concentrations that elicited submaximal production of IL-1ra potentiated IgG-induced IL-lra production. The production of IL-lra and IL-1β are under differential regulation because serum, IgG, and GM-CSF were potent stimuli for the production of IL-1ra but not IL-1β, and the prevention of cell-cell contact of PBMC reduced IL-1ra but not IL-1β production.

Evaluation of alveolar macrophages in normals and individuals with active pulmonary sarcoidosis for the spontaneous expression of the interleukin-1β gene

We have evaluated the hypothesis that the presence of large numbers of activated helper/ inducer T lymphocytes in the lungs of individuals with active pulmonary sarcoidosis is associated with the exaggerated release of interleukin-1 (IL-1) by alveolar macrophages. Evaluation of media from unstimulated cultured sarcoid alveolar macrophages failed to detect IL-1 activity. When parallel cultures of sarcoid and normal alveolar macrophages were stimulated with lipopolysaccharide (LPS), they released similar amounts of IL-1 activity. Using a highly specific polyclonal anti-IL-1β antibody and flow cytometry to evaluate cell-associated IL-1β, analysis of fresh alveolar macrophages from patients with active sarcoidosis and normal individuals revealed no detectable cell-associated IL-1β, but IL-1β was present when macrophages from sarcoid patients and normals were stimulated with LPS. Similar observations were made using immunoblot analysis of cell lysates of the same unstimulated and stimulated macrophages. Finally, Northern analysis of alveolar macrophages for IL-1β mRNA transcripts demonstrated minimal, but equivalent, amounts of IL-1β in both normal and sarcoid macrophages, as compared to the much larger quantities present in LPS-stimulated alveolar macrophages. Thus, while alveolar macrophages of individuals with sarcoidosis are clearly capable of expressing the IL- 1β gene, these findings suggest that altered expression of the IL-1β gene by alveolar macrophages does not play a central role in the exaggerated lung T-cell activation characteristic of sarcoidosis.