Immunopharmacology最新文献

{"title":"The flavonoid baicalin exhibits anti-inflammatory activity by binding to chemokines","authors":"Bao Qun Li ,&nbsp;Tao Fu ,&nbsp;Wang-Hua Gong ,&nbsp;Nancy Dunlop ,&nbsp;Hsiang-fu Kung ,&nbsp;Yaodong Yan ,&nbsp;Jian Kang ,&nbsp;Ji Ming Wang","doi":"10.1016/S0162-3109(00)00244-7","DOIUrl":"10.1016/S0162-3109(00)00244-7","url":null,"abstract":"<div><p><span>Baicalin<span> (BA) is a flavonoid compound purified from the medicinal plant </span></span><span><em>Scutellaria baicalensis</em></span><span><span><span> Georgi and has been reported to possess anti-inflammatory and anti-viral activities. In order to elucidate the mechanism(s) of action of BA, we tested whether BA could interfere with chemokines or </span>chemokine receptors, which are critical mediators of inflammation and infection. We observed that BA inhibited the binding of a number of chemokines to human leukocytes or cells transfected to express specific chemokine receptors. This was associated with a reduced capacity of the chemokines to induce cell migration. Co-injection of BA with </span>CXC chemokine<span><span><span> interleukin-8 (IL-8) into rat skin significantly inhibited IL-8 elicited neutrophil infiltration. BA did not directly compete with chemokines for binding to receptors, but rather acted through its selective binding to chemokine ligands. This conclusion was supported by the fact that BA cross-linked to </span>oxime resin bound chemokines of the CXC (stromal cell-derived factor (SDF)-1α, IL-8), CC (macrophage inflammatory protein (MIP)-1β, monocyte chemotactic protein (MCP)-2), and C (lymphotactin (Ltn)) subfamilies. BA did not interact with </span>CX3C chemokine fractalkine/neurotactin or other cytokines, such as TNF-α and IFN-γ, indicating that its action is selective. These results suggest that one possible anti-inflammatory mechanism of BA is to bind a variety of chemokines and limit their biological function.</span></span></p></div>","PeriodicalId":13327,"journal":{"name":"Immunopharmacology","volume":"49 3","pages":"Pages 295-306"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0162-3109(00)00244-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21829601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of humoral immune responses in the rat by centrally applied Met–Enk and opioid receptor antagonists: functional interactions of brain OP1, OP2 and OP3 receptors","authors":"Mirjana Dimitrijević ,&nbsp;Stanislava Stanojević ,&nbsp;Vesna Kovac̆ević-Jovanović ,&nbsp;Tatjana Miletić ,&nbsp;Vesna Vujić-Redz̆ić ,&nbsp;Jelena Radulović","doi":"10.1016/S0162-3109(00)00213-7","DOIUrl":"10.1016/S0162-3109(00)00213-7","url":null,"abstract":"<div><p><span>We have previously demonstrated that central application of leucine–enkephalin (Leu–Enk) elicits potentiation and suppression of humoral immune responses through OP</span>₁ (δ) and OP₂ (κ) receptors, respectively. Interestingly, both effects were found to be additionally dependent on OP₃<span><span> (μ) receptor function. In the present study, we have further investigated whether opioid receptor interactions underlie the immunomodulatory effects of </span>endogenous opioids as well as exogenously applied methionine–enkephalin (Met–Enk). For that purpose, the plaque-forming cell (PFC) response was determined in rats injected intracerebroventricularly (i.c.v.) with opioid receptor-selective antagonists and Met–Enk. Application of the OP</span>₁<span> antagonist ICI 174864, but not naltrindole, resulted in suppression of the PFC response. In contrast, i.c.v. injection of the OP</span>₂ selective antagonist <em>nor</em>-binaltorphimine (<em>nor</em><span>-BNI) significantly potentiated the PFC response. Both effects, presumably mediated by endogenous opioid peptides, were antagonized by the OP</span>₃<span> receptor antagonist<span> β-funaltrexamine (β-FNA) at a dose that was devoid of immunomodulatory activity. The immunopotentiation of the PFC response induced by Met–Enk was reversed by OP</span></span>₁ receptor antagonists, naltrindole and ICI 174864, but not by β-FNA or <em>nor</em>-BNI.</p><p>On the basis of these and previous findings, it may be concluded that central OP₃ receptors are permissive for the central immunomodulatory action of endogenous opioid peptides and Leu–Enk. In contrast, the central immunoenhancing effect of Met–Enk appears to be mediated through OP₃-independent OP₁ receptors.</p></div>","PeriodicalId":13327,"journal":{"name":"Immunopharmacology","volume":"49 3","pages":"Pages 255-262"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0162-3109(00)00213-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21828527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin 2 maintains biologic stability and sterility over prolonged time","authors":"M Safar,&nbsp;R.P Junghans","doi":"10.1016/S0162-3109(00)00241-1","DOIUrl":"10.1016/S0162-3109(00)00241-1","url":null,"abstract":"<div><p><span>The FDA approved interleukin 2<span> (IL2) for clinical use in 1992 in a high-dose bolus intravenous infusion schedule. IL2 administered by continuous low- and intermediate-dose infusion can result in a variety of immunologic effects including the expansion of the Natural Killer (NK) cell pool and immune reconstitution in immune-deficient hosts. These immune modifications are essential for augmentation of both currently available and evolving </span></span>immunotherapies<span>. The manufacturer's data indicate stability of the IL2 for a period of 6 days. This time frame is not practical for prolonged infusional schemes necessitating frequent changes of drug depots. We tested the biologic stability and sterility of the commercially available recombinant IL2 preparation (aldesleukin; Proleukin, Chiron) under clinical conditions for up to 30 days. Our results confirm that IL2 retains its biologic activity and sterility under these conditions for prolonged periods. This information will simplify IL2 outpatient regimens, allowing for convenient intervals for drug depot renewal, leading to improved patient compliance and conserved health care expenditures.</span></p></div>","PeriodicalId":13327,"journal":{"name":"Immunopharmacology","volume":"49 3","pages":"Pages 419-423"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0162-3109(00)00241-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21830155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevention of collagen-induced arthritis in DBA/1 mice by oral administration of AZ-9, a bacterial polysaccharide from Klebsiella oxytoca","authors":"Ryosuke Sugihara ,&nbsp;Masayasu Yoshimura ,&nbsp;Masaharu Mori ,&nbsp;Naoki Kanayama ,&nbsp;Masaki Hikida ,&nbsp;Hitoshi Ohmori","doi":"10.1016/S0162-3109(00)00247-2","DOIUrl":"10.1016/S0162-3109(00)00247-2","url":null,"abstract":"<div><p><span><span>Collagen-induced arthritis (CIA) is an excellent model of rheumatoid arthritis<span><span> (RA) in humans that is induced in DBA/1 mice immunized with bovine type II collagen (CII). Here, we report that the induction of CIA was effectively suppressed by oral administration of AZ-9, a purified </span>polysaccharide with the average molecular weight of approximately 200 kDa that was produced by a </span></span>soil bacterium, </span><span><em>Klebsiella oxytoca</em></span><span>. When AZ-9 was administered at 125–250 mg/kg/day orally for 9 consecutive days after immunization with CII followed by its administration every 3 days, resulted in a marked reduction of the incidence and the severity of CIA. The serum level of anti-CII IgG2a and the production of IFN-γ and IL-12 in the draining lymph node (LN) cells were significantly lower in AZ-9-administered mice than the untreated control. These findings suggest that orally administered AZ-9 suppressed CIA through attenuating a Th1-type response to CII. AZ-9 could be fragmented into smaller molecules (3–4 kDa) without losing its suppressive activity.</span></p></div>","PeriodicalId":13327,"journal":{"name":"Immunopharmacology","volume":"49 3","pages":"Pages 325-333"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0162-3109(00)00247-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21829604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative study of lymphocyte-suppressive potency between prednisolone and methylprednisolone in rheumatoid arthritis","authors":"Toshihiko Hirano ,&nbsp;Norioki Tsuboi ,&nbsp;Masato Homma ,&nbsp;Kitaro Oka ,&nbsp;Tohru Takekoshi ,&nbsp;Koichiro Tahara ,&nbsp;Hirofumi Takanashi ,&nbsp;Haruo Abe ,&nbsp;Yukitomo Urata ,&nbsp;Tohru Hayashi","doi":"10.1016/S0162-3109(00)00263-0","DOIUrl":"10.1016/S0162-3109(00)00263-0","url":null,"abstract":"<div><p><span>We compared lymphocyte-suppressive potencies of prednisolone<span> and methylprednisolone<span> in rheumatoid arthritis (RA). IC</span></span></span>₅₀<span>s of the glucocorticoids<span> (GCs) on concanavalin A-induced blastogenesis of peripheral-blood mononuclear cells (PBMCs) from 44 RA patients and 30 healthy subjects were estimated in vitro, and differences in the IC</span></span>₅₀s of the two GCs were evaluated. The mean (±SD) IC₅₀s for prednisolone and methylprednisolone on PBMC-blastogenesis of RA were 17.2±17.1 and 12.6±18.4 ng/ml, respectively, and no significant differences were observed between prednisolone-IC₅₀ and methylprednisolone-IC₅₀. In contrast, the mean IC₅₀s of prednisolone and methylprednisolone on healthy PBMCs were 19.4±22.4 and 3.7±3.9 ng/ml, respectively, and thus methylprednisolone potency was significantly higher than prednisolone potency (<em>p</em><span>&lt;0.01). Methylprednisolone potency against PBMCs in RA patients exhibiting a high level of rheumatoid factor (RF) (&gt;20 IU/ml) and the rheumatoid arthritis particle-agglutination value (RAPA) (&gt;80) was significantly higher than that of patients exhibiting a lower level of RF or RAPA (</span><em>p</em>&lt;0.05). In prednisolone-IC₅₀<span>, however, such differences between the two patient-subgroups were not observed. Unlike reported cases of renal transplantation and healthy subjects, there was no difference in the lymphocyte-suppressive potencies for both prednisolone and methylprednisolone on RA-PBMCs. However, PBMCs from RA patients exhibiting high levels of RF or RAPA are more sensitive to methylprednisolone rather than prednisolone.</span></p></div>","PeriodicalId":13327,"journal":{"name":"Immunopharmacology","volume":"49 3","pages":"Pages 411-417"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0162-3109(00)00263-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21830154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ins and outs of getting in: structures and signals that enhance BCR or Fc receptor-mediated antigen presentation","authors":"Li Shen,&nbsp;Mark L Lang,&nbsp;William F Wade","doi":"10.1016/S0162-3109(00)00255-1","DOIUrl":"10.1016/S0162-3109(00)00255-1","url":null,"abstract":"<div><p>Antigen-presenting cells internalize antigen by fluid-phase pinocytosis<span><span><span> or by endocytosis via surface receptors such as the </span>B cell receptor<span><span> (BCR) and Fc receptors for IgG, IgA and IgE (FcR). While both modes of </span>internalization lead to </span></span>antigen presentation<span><span> it is recognized that receptor-mediated endocytosis greatly enhances the efficiency of processing and antigen presentation. Receptors facilitate the entry of antigen into the endocytic pathway by interaction of their internalization motifs with the endocytic machinery. These motifs include tyrosine-based, dileucine and casein kinase-like motifs. However these structures appear insufficient to support processing of cryptic epitopes, leading to a limited immune response. Cryptic epitope processing appears dependent on receptor signaling which is mediated by immunoreceptor tyrosine activation motifs (ITAMs). The signaling cascade which follows receptor crosslinking promotes reorganization and acidification of the late endocytic compartment or MIIC. Signaling events downstream of Syk, in particular </span>calcium flux<span><span> and protein kinase C<span><span> activation, are necessary for MIIC induction. PI(3) kinase is also involved at multiple steps in antigen presentation, including production of PIP3 and transport of cathepsins. PIP3 is crucial both as a binding substrate for proteins implicated in </span>vesicle transport and for the recruitment of signaling molecules to the plasma membrane. Among PIP3 activated molecules, </span></span>protein kinase B (PKB) has been linked to endocytic function. We observe association of activated PKB with the MIIC after signaling through antigen presentation-competent receptors, but not mutant, presentation-defective receptors.</span></span></span></p></div>","PeriodicalId":13327,"journal":{"name":"Immunopharmacology","volume":"49 3","pages":"Pages 227-240"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0162-3109(00)00255-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21828524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intratracheal administration of anaphylatoxin C5a potentiates antigen-induced pulmonary reactions through the prolonged production of cysteinyl–leukotrienes","authors":"Mamoru Kodani ,&nbsp;Noriyuki Sakata ,&nbsp;Yukio Takano ,&nbsp;Hiro-o Kamiya ,&nbsp;Takeshi Katsuragi ,&nbsp;Tony E Hugli ,&nbsp;Masayoshi Abe","doi":"10.1016/S0162-3109(00)00240-X","DOIUrl":"10.1016/S0162-3109(00)00240-X","url":null,"abstract":"<div><p><span>The effects of intratracheal administration of anaphylatoxin C5a<span> on airway inflammation have been studied using two sources of material, </span></span>zymosan<span><span> activated serum (ZAS) and purified rat C5a des Arg, in order to determine the influence of </span>complement activation<span> on allergic airway disorders.</span></span></p><p><span>The intratracheal administration of ovalbumin (OA) to OA-sensitized rats generated two phases of airway response, an immediate airway response (IAR) occurring within 15 min and a late airway response (LAR) beginning 4–6 h after the allergen challenge. The simultaneous administration of ZAS and OA into the trachea generated a sustained elevation of airway resistance (Raw) following IAR, while that of OA or ZAS alone resulted in Raw returning nearly to the baseline just after the IAR. The elevation of Raw after the combined challenge of OA and ZAS was significantly inhibited by pretreatment with a CysLT</span>₁<span><span> receptor antagonist, </span>pranlukast 30 mg/kg, but after that OA or ZAS alone was not significantly inhibited by pranlukast. The intratracheal administration of purified C5a produced an airway response that was similar to, but higher than, that evoked by ZAS. Namely, the challenge with OA plus C5a resulted in a higher IAR than OA plus ZAS, and also caused an early animal death up to 6 h, which was prevented by a combined pretreatment with pranlukast and the H</span>₁<span> receptor antagonist, diphenhydramine.</span></p><p><span><span>A histological examination at 6 h after the OA challenge identified an infiltration of inflammatory cells into the bronchial submucosal tissue, with a predominance of neutrophils and fewer </span>eosinophils. On the other hand, a histological examination after the OA and ZAS challenge showed more severe infiltration of granulocytes into the bronchial submucosal tissue than that with OA or ZAS alone. The challenge with OA plus C5a was associated with severe perivascular leakage in the lungs and the combined pretreatment with both the antagonists led to a marked reduction in perivascular leakage. The quantitation of </span><em>N</em>-acetyl-leukotriene E₄ (<em>N</em>-Ac-LTE₄), a major metabolite of cysteinyl–leukotrienes (cysLTs), in the bile indicated a significantly greater and longer excretion of cysLTs, from 1 to 6 h after the combined challenge, than that after either OA or ZAS alone. This suggested a prolonged generation of cysLTs in the lung by the combined challenge.</p><p>In conclusion, our findings suggest that anaphylatoxin C5a may mediate the airway inflammatory response induced by a specific antigen challenge partly through a prolonged production of cysLTs and the release of histamine.</p></div>","PeriodicalId":13327,"journal":{"name":"Immunopharmacology","volume":"49 3","pages":"Pages 263-274"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0162-3109(00)00240-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21828528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential effects of pentoxifylline, a non-specific phosphodiesterase inhibitor, on the production of IL-10, IL-12 p40 and p35 subunits by murine peritoneal macrophages","authors":"Janusz Marcinkiewicz ,&nbsp;Agnieszka Grabowska ,&nbsp;Ryszard Lauterbach ,&nbsp;Malgorzata Bobek","doi":"10.1016/S0162-3109(00)00249-6","DOIUrl":"10.1016/S0162-3109(00)00249-6","url":null,"abstract":"<div><p><span><span>Pentoxifylline (PTX), a </span>methylxanthine derivative<span>, has been reported to be an effective drug in inhibiting TNF-α responses during septic shock. The inhibition of TNF-α production seems to be correlated with increased intracellular cAMP levels. PTX also affects the production of other cytokines such as IL-1, IL-6, IL-10, IL-12, and IFN-γ. However, inhibition, as well as enhancement of </span></span>cytokine production, has been observed in vitro, depending on the PTX concentration and cell type used.</p><p><span>IL-12 is a heterodimeric cytokine that plays an important role in the development of Th1-mediated inflammatory responses. IL-12 along with TNF-α and other proinflammatory cytokines has shown to be responsible for the pathological reaction, which may lead to septic shock. For biological activity, the expression of both subunits of IL-12, p35 and p40, is required. Moreover, the p40 chain of IL-12 specifically inhibits the effects of the IL-12 </span>heterodimer.</p><p>In this study, we investigated the effects of PTX on the production of both proinflammatory (TNF-α, IL-6, IL-12) and anti-inflammatory (IL-10) cytokines by murine macrophages (Mφ). We have found that PTX, at concentrations below 100 μg/ml, selectively inhibited the production of TNF-α. Forskolin, a cAMP-elevating agent, similarly affected the production of the cytokines tested. However, at higher concentrations, PTX inhibited the production of TNF-α, IL-10, and IL-12 p35, but surprisingly, PTX enhanced the production of IL-12 p40. Concentrations of IL-10 were negatively correlated with the concentrations of IL-12 p40 subunit. These results further confirm the relevance of the use of PTX in clinical trials of immunological disorders characterised by inappropriate Th1 type immune responses.</p></div>","PeriodicalId":13327,"journal":{"name":"Immunopharmacology","volume":"49 3","pages":"Pages 335-343"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0162-3109(00)00249-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21829605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of low-dose prednisone in vivo on the ability of complement receptor to mediate an oxidative burst in rat neutrophils","authors":"Cleni M Marzocchi-Machado ,&nbsp;Elisa Maria S Russo ,&nbsp;Celene Maria O.S Alves ,&nbsp;Ana Cristina M Polizello ,&nbsp;Ana Elisa C.S Azzolini ,&nbsp;Yara Maria Lucisano-Valim","doi":"10.1016/S0162-3109(00)00204-6","DOIUrl":"10.1016/S0162-3109(00)00204-6","url":null,"abstract":"<div><p><span><span>Glucocorticoids<span> have been used in the treatment of a variety of inflammatory processes including autoimmune diseases. However, the influence of low-dose glucocorticoids on the respiratory burst activity of neutrophils<span> has not been studied. The aim of this work was to study the effect of treatment with low-dose prednisone on the oxidative burst of rat peripheral blood neutrophils. Wistar male rats were treated with prednisone by gavage (28, 87 or 257 μg/animal/day) for 7 or 15 days. These doses are equivalent to 10, 30 or 90 mg/adult human (∼70 kg)/day, respectively. Sera from normal rats were used to opsonize </span></span></span>zymosan (opZy). Neutrophils (1×10</span>⁵<span>) were stimulated by opZy and the oxidative burst of control or treated rat cells was measured by luminol-dependent chemiluminescence<span><span> (CL). Prednisone did not affect the CL of rat neutrophils for either period of treatment, or any studied doses, when compared with controls. These results suggest that the low-dose prednisone has no effect on the oxidative burst mediated by complement receptors during the rat neutrophil </span>phagocytosis of complement-opZy.</span></span></p></div>","PeriodicalId":13327,"journal":{"name":"Immunopharmacology","volume":"49 3","pages":"Pages 247-254"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0162-3109(00)00204-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21828526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of a ceramide analog, N-acetylsphingosine on the induction of proliferation and IL-2 synthesis in T cells from young and old F344 rats","authors":"Mohammad A Pahlavani ,&nbsp;Danial M Vargas","doi":"10.1016/S0162-3109(00)00254-X","DOIUrl":"10.1016/S0162-3109(00)00254-X","url":null,"abstract":"<div><p><span>Ceramide is a physiological mediator of extracellular signals that control various cellular functions, including proliferation and apoptosis. In the present study, we examined the effects of cell-permeable ceramide analog, </span><em>N</em>-acetyl-sphingosine (C₂<span><span>-ceramide) on the induction of proliferation and interleukin-2 (IL-2) synthesis in T cells from young and old rats. Splenic T cells from 6- and 24-month-old </span>Fischer 344 rats were treated with C</span>₂-ceramide and then incubated with anti-CD3 antibody for 24 or 48 h. The induction of proliferation and IL-2 production by anti-CD3 was significantly (<em>P</em>&lt;0.001) lower in T cells from old rats compared to T cells from young rats. C₂-ceramide treatment resulted in suppression of proliferation and IL-2 production in a concentration-dependent manner. The suppressive effect of C₂<span>-ceramide on proliferation and IL-2 production was greater in T cells from old rats than T cells from young rats. We investigated whether this decreased responsiveness was due to induction of program cell death (apoptosis) and found that there was a significant increase in DNA fragmentation in C</span>₂-ceramide treated and anti-CD3 stimulated T cells from both young and old rats. The increase in DNA fragmentation was paralleled with an increase in caspase-3 activation. C₂-ceramide-induced caspase-3 activation and DNA fragmentation was significantly (<em>P</em><span>&lt;0.5) higher in stimulated T cells from old rats compared to stimulated T cells from young rats. These results suggest that the sphingomyelin-ceramide signaling pathway may play an important regulatory role in the well-documented age-related decline in immune function.</span></p></div>","PeriodicalId":13327,"journal":{"name":"Immunopharmacology","volume":"49 3","pages":"Pages 345-354"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0162-3109(00)00254-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21829606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}