International journal of immunopharmacology最新文献

{"title":"Influence of melatonin on immunotoxicity of lead","authors":"Young-Ok Kim ,&nbsp;Myoung-Yun Pyo ,&nbsp;Joung-Hoon Kim","doi":"10.1016/S0192-0561(00)00043-6","DOIUrl":"10.1016/S0192-0561(00)00043-6","url":null,"abstract":"<div><p><span>The results suggested that immunotoxicity induced by lead [Pb, as Pb(NO</span>₃)₂<span><span>] was significantly restored or prevented by melatonin<span> (MLT). MLT (10 or 50 mg/kg) was orally administered to ICR mice<span> daily for 28 days, and Pb was also administered at 35 mg/kg in the same way 2 h after the administration of MLT, and the normal mice were given vehicle. Within the Pb plus MLT-treated group, the body weight gains and the relative thymus weights were significantly increased when compared with the treatment of Pb alone. The relative spleen and liver weights were increased by the treatment of Pb alone, and then restored to normal value by MLT treatment. </span></span></span>Hemagglutination<span> (HA) titer, plaque-forming cell response to sheep red blood cell<span><span> (SRBC), and secondary IgG antibody response to BSA were significantly enhanced in the Pb plus MLT-treated mice, as opposed to when compared with the treatment of Pb alone. The </span>mitogenic response<span><span> of splenic T cell<span> to concanavalin A and that of B cells to </span></span>lipopolysaccharide was remarkably increased by MLT treatment when compared with treatment of Pb alone. Splenic CD4</span></span></span></span>⁺cells were significantly increased by MLT treatment when compared with treatment of Pb alone. In case of CD8⁺<span> cells, the slight enhancement was observed in MLT treatment. Splenic T and B cells were significantly increased by MLT treatment when compared with the treatment of Pb alone. The natural killer cell, phagocytic activity and the number of peripheral leukocytes were significantly enhanced in Pb plus MLT-treated mice when compared with the treatment of Pb alone.</span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 10","pages":"Pages 821-832"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00043-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21798907","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 anti-allergic drug histaglobin inhibits NF-κB nuclear translocation and down-regulates proinflammatory cytokines","authors":"Mohamed Ayoub ,&nbsp;Klaus Mittenbühler ,&nbsp;Bernd W Sütterlin ,&nbsp;Wolfgang G Bessler","doi":"10.1016/S0192-0561(00)00037-0","DOIUrl":"10.1016/S0192-0561(00)00037-0","url":null,"abstract":"<div><p><span><span><span><span>The transcription factor NF-κB is the central regulator for the expression of various genes involved in inflammation, infection and immune response including the genes for IL-1β, TNF-α, IL-6 and leukocyte adhesion molecules. Here, we show that the anti-allergic drug histaglobin down-regulates the release of IL-1β, TNF-α, IL-6 and IL-10 in human </span>peripheral blood mononuclear cell cultures. This down-regulatory effect becomes even more pronounced when the cultures are simultaneously activated with the T-lymphocyte </span>mitogen </span>phytohemagglutinin<span> (PHA) or with the B-lymphocyte and macrophage activator lipopeptide (P</span></span>₃CSK₄<span>). We also demonstrate that histaglobin inhibits the nuclear translocation of NF-κB in response to TNF-α or lipopolysaccharide<span> (LPS) in bone marrow-derived macrophages of Balb/c mice. The inhibitory effect of histaglobin on NF-κB activation and cytokine release might be responsible for its anti-allergic effect as demonstrated in clinical studies.</span></span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 10","pages":"Pages 755-763"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00037-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21798901","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":"Comparison of inhibitory effects of local anesthetics on immune functions of neutrophils","authors":"Yasutaka Azuma,&nbsp;Mitsuko Shinohara,&nbsp;Pao-Li Wang,&nbsp;Yuichi Suese,&nbsp;Hideki Yasuda,&nbsp;Kiyoshi Ohura","doi":"10.1016/S0192-0561(00)00040-0","DOIUrl":"10.1016/S0192-0561(00)00040-0","url":null,"abstract":"<div><p>Immunological effects of a variety of local anesthetics<span> on adhesion, phagocytosis<span><span>, and the production of superoxide anion and hydrogen peroxide by neutrophils<span> were compared. Neutrophils were isolated by peritoneal lavage from rats, 4 h after injection of 1% glycogen. Lidocaine, mepivacaine, </span></span>procaine<span>, prilocaine<span> and tetracaine at 1 mg/ml inhibited adhesion, phagocytosis, and the production of superoxide anion and hydrogen peroxide in neutrophils. Moreover, lidocaine, mepivacaine, procaine and prilocaine at 0.1 mg/ml inhibited the production of superoxide anion and hydrogen peroxide but not adhesion or phagocytosis. In contrast, tetracaine at 0.1 mg/ml inhibited phagocytosis, and the production of superoxide anion and hydrogen peroxide but not adhesion. At 0.01 mg/ml, however, tetracaine inhibited the production of superoxide anion and hydrogen peroxide; in contrast, other drugs failed to affect neutrophil function. These results suggest that the local anesthetics may affect adhesion, phagocytosis, and the production of superoxide anion and hydrogen peroxide by neutrophils.</span></span></span></span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 10","pages":"Pages 789-796"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00040-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21798904","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":"Inhibition of basophil histamine release by tyrosine kinase and phosphatidylinositol 3-kinase inhibitors","authors":"A Tedeschi,&nbsp;M Lorini,&nbsp;S Galbiati,&nbsp;S Gibelli,&nbsp;A Miadonna","doi":"10.1016/S0192-0561(00)00041-2","DOIUrl":"10.1016/S0192-0561(00)00041-2","url":null,"abstract":"<div><p><span>It has been demonstrated that tyrosine kinase<span> (TK) and phosphatidylinositol 3-kinase (PI3-K) are involved in IgE-mediated stimulation of human basophils<span>; conversely, little is known about the biochemical pathways activated by IL-3 and GM-CSF. The aim of this study was to evaluate the effects of TK and PI3-K inhibitors on basophil histamine release induced by anti-IgE, IL-3 and GM-CSF. Since IL-3 and GM-CSF cause histamine release from normal human basophils only when the inhibitory effect of extracellular Na</span></span></span>⁺ has been removed, peripheral blood leukocytes were suspended in isotonic solutions containing either 140 mM NaCl or 140 mM <em>N</em>-methyl-<span>D</span>-glucamine⁺<span><span><span>. After stimulation with anti-IgE, IL-3 or GM-CSF, histamine release was measured by an automated fluorometric method. The effects of preincubation with four different TK inhibitors (AG-126, </span>genistein, </span>lavendustin A<span>, tyrphostin 51) and one PI3-K inhibitor (wortmannin) were evaluated. AG-126, genistein and lavendustin A exerted a significant dose-dependent inhibitory effect on basophil histamine release induced by anti-IgE (either in high or in low Na</span></span>⁺ medium), IL-3 and GM-CSF. Among the TK inhibitors, lavendustin A exerted the most potent activity, followed by AG-126 and genistein. Tyrphostin 51 caused a weak inhibition of histamine release induced by IL-3, GM-CSF and anti-IgE in a low Na⁺ medium, but not in a physiological Na⁺<span>-containing medium. The PI3-K inhibitor wortmannin<span> exerted the most effective inhibitory activity on the histamine release induced by the three agonists. The combined effects of lavendustin A and wortmannin were less than additive, suggesting that TK and PI3-K are involved in the same activation pathway in human basophils. These results suggest a possible role of TK and PI3-K in basophil histamine release induced by anti-IgE, IL-3 and GM-CSF. TK and PI3-K are indeed potential therapeutic targets for antiallergic drugs.</span></span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 10","pages":"Pages 797-808"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00041-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21798905","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":"In vivo acute depletion of CD8+ T cells before murine cytomegalovirus infection upregulated innate antiviral activity of natural killer cells","authors":"Mohamad Labib Salem ,&nbsp;Mohammad Sohrab Hossain","doi":"10.1016/S0192-0561(00)00033-3","DOIUrl":"10.1016/S0192-0561(00)00033-3","url":null,"abstract":"<div><p>In this study, we investigated the effect of depletion of CD8⁺<span> T cells on the activity of natural killer (NK) cells at an early phase of murine cytomegalovirus (MCMV) infection. For CD8</span>⁺<span> T cell depletion<span>, mice were intraperitoneally treated with anti-CD8 mAb, purified from 2.43 hybridoma, for 2 consecutive days before or after infection. Three days after infection, we found that an acute depletion of CD8</span></span>⁺<span> T cells before infection caused a significant decrease in the viral load in liver and spleen. This effect coincided with an increase in numbers of CD3</span>⁻ NK1.1⁺<span> cells in spleen and their expression of the early activation molecule CD69<span>. Although cytolytic activity of NK cells increased on day 3 of infection in CD8-depleted mice, the level of IFN-γ decreased in serum and supernatant of cultured spleen cells. In contrast to the effect of acute depletion of CD8</span></span>⁺ T cells before infection, the depletion after infection had no effect on the viral load or number and cytolytic function of NK cells. Lack of effects of CD8⁺ T cell depletion on the viral load and NK cytolytic activity is also observed in CD8⁺<span> knockout mice. In conclusion, the results suggest that an acute depletion of CD8</span>⁺<span> T cells before MCMV infection effectively upregulated the antiviral activity of NK cells. This effect appears to be mediated through an increase in numbers, activation and cytolytic activity of NK cells.</span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 9","pages":"Pages 707-718"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00033-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21726579","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 1β and GABA-transaminase activity in rat thymus","authors":"D. Cavallotti ,&nbsp;M. Artico ,&nbsp;C. Cavallotti ,&nbsp;S. De Santis ,&nbsp;F.Tranquilli Leali","doi":"10.1016/S0192-0561(00)00035-7","DOIUrl":"10.1016/S0192-0561(00)00035-7","url":null,"abstract":"<div><p><span>The occurrence and distribution of 4-aminobutyrate:2 oxoglutarate transaminase (GABA-t) activity were examined in the rat thymus of normal and immunostimulated rats using biochemical and histoenzymatical methods. Specific GABA-t reactivity was confined primarily to the arteries and, to a lesser extent, to the veins. Only a few activities could be observed in association with the subcapsular and medullar part of the parenchyma and nerve fibers. GABA-t was considered a linking enzyme between the immune and the nervous system and it was studied with the aim of analyzing the relationships between these two systems. Our findings indicate that the GABA-t activity in the thymus is specifically located in the wall of the blood vessels. Moreover, our results demonstrate the presence of a GABA-t activity in the peripheral blood vessels. Treatment with </span>interleukin 1β induces an increase of protein content of the amounts of GABA-t biochemically assayed and of the levels of histoenzymatically stained GABA-t. Furthermore, staining of the different structures of the thymus in treated or untreated rats shows that the significant modifications concern the parenchyma, the structures resembling nerve fibers and finally, the whole thymus. On the contrary, the highest activity of the GABA-t is located in the walls of arteries, veins and lymphatic vessels.</p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 9","pages":"Pages 719-728"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00035-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21726578","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":"Hydroxyzine inhibits experimental allergic encephalomyelitis (EAE) and associated brain mast cell activation","authors":"Violetta Dimitriadou ,&nbsp;Xinzhu Pang ,&nbsp;Theoharis C Theoharides","doi":"10.1016/S0192-0561(00)00029-1","DOIUrl":"10.1016/S0192-0561(00)00029-1","url":null,"abstract":"<div><p><span><span><span><span><span><span>Experimental allergic encephalomyelitis (EAE) has been used as an animal model for the human </span>demyelinating disease<span> multiple sclerosis<span> (MS). In acute MS or EAE, early disruption in the integrity of the blood–brain-barrier (BBB) precedes brain infiltration by inflammatory cells or any clinical evidence of disease. BBB permeability could be affected by vasoactive mediators and cytokines released from perivascular brain mast cells. We investigated the number and degree of activation of brain mast cells in EAE and the effect of the heterocyclic histamine-1 receptor antagonist </span></span></span>hydroxyzine, a </span>piperazine<span> compound known to also block mast cells. Acute EAE was induced in Lewis rats by immunization with whole guinea pig spinal cord homogenate and complete Freund’s adjuvant (CFA). A second group of animals were treated orally with hydroxyzine for one day before immunization and then continuously for 14 days. Control rats were treated with CFA or hydroxyzine alone. The clinical progression of EAE was assessed on days 10, 12 and 14 after immunization. The number of metachromatic mast cells and the degree of </span></span>degranulation<span> was assessed in the thalamus with light microscopy<span>. At day 14, there was a three-fold increase in the number of brain mast cells with EAE, as compared to controls. These cells were positive for the immunoglobulin E binding protein (FcϵRI), while those from control rats were not. Over 40% of all thalamic mast cells studied in EAE showed partial staining or extruded </span></span></span>secretory granule indicative of secretion. Hydroxyzine treatment inhibited (</span><em>p</em><span>&lt;0.05) the progression and severity of EAE by 50% and the extent of mast cell degranulation by 70% (</span><em>p</em>&lt;0.05). These findings indicate that brain mast cells are associated with EAE development and that inhibition of their activation correlates positively with the clinical outcome.</p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 9","pages":"Pages 673-684"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00029-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21726064","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":"Inhibitory effect of sodium salicylate on nitric oxide production from TM4 Sertoli cells","authors":"Cha-Kwon Chung ,&nbsp;Hyun-Na Koo ,&nbsp;Kwang-Yoll Chung ,&nbsp;Taekyun Shin ,&nbsp;Hyung-Ryong Kim ,&nbsp;Han-Jung Chae ,&nbsp;Nyeon-Hyoung An ,&nbsp;Cheorl-Ho Kim ,&nbsp;Hyung-Min Kim","doi":"10.1016/S0192-0561(00)00031-X","DOIUrl":"10.1016/S0192-0561(00)00031-X","url":null,"abstract":"<div><p>Nitric oxide<span> (NO) has been proposed to play a role in a variety of inflammatory diseases<span><span><span>. Sodium salicylate (NaSal) is the most commonly used anti-inflammatory agent. We investigated whether NaSal can diminish the production of NO in TM4 Sertoli cells. TM4 Sertoli cells produced a small amount of NO upon treatment with recombinant interferon-γ (rIFN-γ). The effect of rIFN-γ was enhanced markedly by the addition of recombinant TNF-α (rTNF-α) in a dose-dependent manner. NaSal (10 and 20 mM) significantly inhibited NO production from TM4 Sertoli cells induced by rIFN-γ plus rTNF-α. In addition, rIFN-γ in combination with rTNF-α showed a marked increase of the expression of </span>inducible NO synthase<span><span> (iNOS) protein. Western blot analysis revealed that NaSal (10 and 20 mM) blocked a step of iNOS </span>protein synthesis. The rIFN-γ plus rTNF-α-induced nuclear factor-κB (NF-κB) activation was significantly blocked by NaSal (10 and 20 mM). On the other hand, neither </span></span>staurosporine<span><span> nor polymyxin B significantly inhibited NO production from TM4 Sertoli cells induced by rIFN-γ plus rTNF-α. The present results indicate that NaSal inhibits rIFN-γ plus rTNF-α-induced NO production in TM4 Sertoli cells via the </span>signal transduction pathway of NF-κB activation.</span></span></span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 9","pages":"Pages 685-692"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00031-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21726065","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":"Synergistic anti-tumor activity of a novel immunomodulator, BCH-1393, in combination with cyclophosphamide","authors":"S. Kadhim,&nbsp;C. Penney,&nbsp;M. Lagraoui,&nbsp;J. Heibein,&nbsp;G. Attardo,&nbsp;B. Zacharie,&nbsp;T. Connolly,&nbsp;L. Gagnon","doi":"10.1016/S0192-0561(00)00028-X","DOIUrl":"10.1016/S0192-0561(00)00028-X","url":null,"abstract":"<div><p><em>N</em>,<em>N</em>-dimethylaminopurine pentoxycarbonyl <span>D</span><span><span>-arginine (BCH-1393) is a novel low molecular weight synthetic immunomodulator that has been shown to significantly stimulate cytotoxic T-lymphocyte responses both in vitro and in vivo (Zacharie B, Gagnon L, Attardo G, Connolly TP, St-Denis Y, Penney CL. Synthesis and activity of 6-substituted purine<span> linker amine immunostimulants. J. Med. Chem. 1997;40:2883–94). Prompted by this evidence, we extended evaluation of BCH-1393 for </span></span>anticancer activity<span><span> in syngeneic mouse </span>experimental tumor models. Consistent with previous findings, in vitro assessment of BCH-1393 activity demonstrated a significant increase in the CTL responses in the range of 10</span></span>⁻⁹–10⁻⁵<span> M. Treatment of mice with four consecutive daily intraperitoneal injections<span><span><span><span> at 25 and 50 mg/kg resulted in a significant increase of the relative percentage of blood CD4+, CD8+, NK and monocyte subsets without any evidence of toxicity. In vivo anti-tumor activity of BCH-1393 was evaluated, either alone or in combination with subtherapeutic doses of </span>cyclophosphamide (Cy), against weakly immunogenic mouse </span>breast carcinoma DA-3 and strongly immunogenic </span>colon adenocarcinoma<span> MC38. Daily intraperitoneal injection of BCH-1393 at 50 mg/kg alone was well tolerated but produced a relatively weak anti-tumor effect in both tumor models. However, a significant inhibition of tumor outgrowth and suppression of established tumor growth was observed when BCH-1393 was administered in combination with subtherapeutic doses of Cy. Combination treatment of 50 mg/kg BCH-1393 with 100 mg/kg Cy (given as single intravenous bolus injection) starting 2 days prior to DA-3 tumor cell inoculation prevented tumor outgrowth in 70–80% of treated mice. In the remaining 20–30% of mice that had developed tumors, a nearly complete (90%) tumor growth inhibition was observed at days 22–24 post tumor implant. In the MC38 tumor model, combination treatment of established tumors with BCH-1393 and Cy (CTX) at 50 mg/kg resulted in a significant delay in tumor growth compared to CTX treatment alone. The observed concomitant anti-tumor activity of BCH-1393 with cyclophosphamide warrants further investigation of this immunomodulator as an adjunctive treatment of cancer.</span></span></span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 9","pages":"Pages 659-671"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00028-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21726063","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 all-trans-retinoic acid on cytokine production in a murine macrophage cell line","authors":"Judy S. Mathew,&nbsp;Raghubir P. Sharma","doi":"10.1016/S0192-0561(00)00032-1","DOIUrl":"10.1016/S0192-0561(00)00032-1","url":null,"abstract":"<div><p>All-<em>trans</em><span>-retinoic acid (RA) is a cancer chemopreventive agent<span><span><span><span> and a pluripotent morphogen. It belongs to the class of </span>retinoids that, besides being inducers of differentiation and growth-inhibitos, exert immunomodulatory and anti-inflammatory functions by mechanisms that are not clearly understood. Macrophages play different roles in diverse </span>physiological processes, including ones in orchestrating immune and inflammatory responses. Products of activated macrophages such as interleukin-1β (IL-1β), </span>tumor necrosis factor α<span><span><span> (TNFα), interleukin-6, interleukin-8, and nitric oxide (NO) are important regulators of inflammatory reactions. In this study J774A.1 cells, a murine </span>macrophage cell line<span>, was used to study the effects of RA on the production of NO, TNFα and IL-1β. Cells were stimulated with lipopolysaccharide (LPS) with or without RA. RA depressed the levels of NO in a dose-dependent manner. NO production and subsequent nitrite accumulation in the media peaked at 24 h, plateaued at 48 h, and remained at the same level through 72 h. The presence of RA decreased TNFα levels, measured by both bioassay and enzyme-linked immunosorbent assay (ELISA), but these did not correlate with increased mRNA expression measured by reverse-transcriptase polymerase chain reaction at 6 h after LPS stimulation. IL-1β protein production measured by both ELISA and bioassay decreased with RA treatment. IL-1β mRNA expression was not affected by RA except at low doses. This study indicated that RA modulates </span></span>cytokine production in J774A.1 macrophage cells. Inhibition of inflammatory cytokine production may play a role in the anti-inflammatory activity of RA. The results suggested that effects of RA are complex and are time and concentration dependent.</span></span></span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 9","pages":"Pages 693-706"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00032-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21726066","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}