Results in immunologyPub Date : 2012-01-01Epub Date: 2012-03-01DOI: 10.1016/j.rinim.2012.02.003
Erin E. Sandford , Megan Orr , Mandy Shelby , Xianyao Li , Huaijun Zhou , Timothy J. Johnson , Subhashinie Kariyawasam , Peng Liu , Lisa K. Nolan , Susan J. Lamont
{"title":"Leukocyte transcriptome from chickens infected with avian pathogenic Escherichia coli identifies pathways associated with resistance","authors":"Erin E. Sandford , Megan Orr , Mandy Shelby , Xianyao Li , Huaijun Zhou , Timothy J. Johnson , Subhashinie Kariyawasam , Peng Liu , Lisa K. Nolan , Susan J. Lamont","doi":"10.1016/j.rinim.2012.02.003","DOIUrl":"10.1016/j.rinim.2012.02.003","url":null,"abstract":"<div><p>Avian pathogenic <em>Escherichia coli</em> (APEC) causes colibacillosis, which is responsible for morbidity and mortality in chickens. Gene expression patterns have previously been demonstrated to differ between chicken populations that are resistant vs. susceptible to bacterial infection, but little is currently known about gene expression response to APEC. Increased understanding of gene expression patterns associated with resistance will facilitate genetic selection to increase resistance to APEC. Male broiler chicks were vaccinated at 2 weeks of age and challenged with APEC at 4 weeks of age. Peripheral blood leukocytes were collected at 1 and 5 day post-infection. Lesions on the liver, pericardium, and air sacs were used to assign a mild or severe pathology status to non-vaccinated, challenged chicks. Ten treatment groups were therefore generated with <em>a priori</em> factors of vaccination, challenge, day post-infection, and the <em>a posteriori</em> factor of pathology status. Global transcriptomic response was evaluated using the Agilent 44K chicken microarray. APEC infection resulted in more up-regulation than down-regulation of differentially expressed genes. Immune response and metabolic processes were enriched with differentially expressed genes. Although vaccination significantly reduced lesions in challenged bird, there was no detectable effect of vaccination on gene expression. This study investigated the transcriptomic differences in host responses associated with mild vs. severe pathology, in addition to the effects of vaccination and challenge, thus revealing genes and networks associated with response to APEC and providing a foundation for future studies on, and genetic selection for, genetic resistance to APEC.</p></div>","PeriodicalId":89845,"journal":{"name":"Results in immunology","volume":"2 ","pages":"Pages 44-53"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinim.2012.02.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31985011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Results in immunologyPub Date : 2012-01-01Epub Date: 2012-04-07DOI: 10.1016/j.rinim.2012.03.003
A. Siah , P. McKenna , J.M. Danger , G. Johnson , F.C.J. Berthe
{"title":"Expression of RAS-like family members, c-jun and c-myc mRNA levels in neoplastic hemocytes of soft-shell clams Mya arenaria using microsphere-based 8-plex branched DNA assay","authors":"A. Siah , P. McKenna , J.M. Danger , G. Johnson , F.C.J. Berthe","doi":"10.1016/j.rinim.2012.03.003","DOIUrl":"10.1016/j.rinim.2012.03.003","url":null,"abstract":"<div><p>The molecular mechanisms by which disseminated neoplasia (DN) is developed in soft shell clams <em>Mya arenaria</em> remain largely unknown. This study aims at quantifying Rho-like GTPase, RAS-Rho, RAS-related C3 botulinum (RAS C3), c-jun as well as c-myc transcript levels in clams sampled at North River (Charlottetown, Prince Edward Island, Canada). The transcripts were quantified using multiplex gene analysis (Quantigene<sup>®</sup> 2 Plex, Affymetrix) in 3 groups of clams: (1) Group C (healthy clams considered as control) with a low percentage of tetraploid hemocytes (<10%); (2) Group D (disease in development): individuals presenting a percentage of tetraploid cells ranging between 10% and 50%; (3) Group E (established disease): clams with a high percentage of tetraploid hemocytes (>50%). Data showed a down-regulation of Rho-like GTPase, Rho-like subfamily, RAS C3, c-jun and an up-regulation of c-myc gene expression. It is believed that a deregulation of the expression of these genes could partly unravel the molecular mechanisms involved in the development of DN in soft shell clams <em>Mya arenaria</em>. Further investigations should be pursued to determine the role of these gene products in clams' hemocytes.</p></div>","PeriodicalId":89845,"journal":{"name":"Results in immunology","volume":"2 ","pages":"Pages 83-87"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinim.2012.03.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31984444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Results in immunologyPub Date : 2012-01-01Epub Date: 2012-01-31DOI: 10.1016/j.rinim.2012.01.003
Shiro Sameshima, Miki Nakao, Tomonori Somamoto
{"title":"Diversity of CD2 subfamily receptors in cyprinid fishes","authors":"Shiro Sameshima, Miki Nakao, Tomonori Somamoto","doi":"10.1016/j.rinim.2012.01.003","DOIUrl":"10.1016/j.rinim.2012.01.003","url":null,"abstract":"<div><p>CD2 family receptor (CD2f) is evolutionarily conserved and is widely expressed by various types of leukocytes. To elucidate the phylogenetic diversity of the CD2f, we characterized CD2f in teleosts using ginbuna crucian carp and zebrafish. The identified CD2f isoforms of the ginbuna carp (caauCD2f) exhibited high sequence similarity to the mammalian CD2 subsets CD48, CD244, and CD319, but it was difficult to classify them into their respective mammalian CD2f based on sequence similarity, the presence of an immunoreceptor tyrosine-based switch motif (ITSM), and phylogenetic tree analysis. Although the four caauCD2f isoforms share an extracellular domain with quite high identity (83–94% identity at the nucleic acid level), they differ in the number of ITSM motifs in their cytoplasmic tail. RT-PCR and <em>in situ</em> hybridization analyses showed that the caauCD2f isoforms are expressed by different cell populations, suggesting that they, like mammalian CD2f, have diverse roles. Interestingly, immunoglobulin (Ig) domain-like sequences with high identity to caauCD2fs are clustered close together within 0.6<!--> <!-->Mbp on zebrafish chromosomes 1 and 2 (at least 8 and 35 sequences, respectively), and many pairs of the Ig domains share more than 90% identity at the amino acid level. Therefore, the teleost CD2fs with considerably high identity have been probably generated from a common ancestral Ig-domain gene by a very recent gene duplication event. These findings suggest that the identified CD2f acquired functional diversification through successive duplications together with the acquisition of ITSM.</p></div>","PeriodicalId":89845,"journal":{"name":"Results in immunology","volume":"2 ","pages":"Pages 25-34"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinim.2012.01.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31985009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Results in immunologyPub Date : 2012-01-01Epub Date: 2011-12-17DOI: 10.1016/j.rinim.2011.12.001
Victoria L. Green, Anna Michno, John Greenman, Nicholas D. Stafford
{"title":"Effect of treatment on systemic cytokines in head and neck squamous cell carcinoma patients","authors":"Victoria L. Green, Anna Michno, John Greenman, Nicholas D. Stafford","doi":"10.1016/j.rinim.2011.12.001","DOIUrl":"10.1016/j.rinim.2011.12.001","url":null,"abstract":"<div><p>The aim of this study was to determine the effect of HNSCC tumour treatment on systemic Th1 and Th2 cytokine levels and investigate correlations with clinicopathological parameters. IL2, IL4, IL5, IL6, IL8, IL10, IL13, GMCSF, IFNγ and TNFα were measured in the serum of 101 newly-presenting HNSCC patients (9 oral cavity, 27 oropharynx, 57 laryngopharynx, 1 sinonasal, 1 parotid and 6 unknown), prior to and following treatment, using a Quantibody<sup>®</sup> array based multiplex sandwich ELISA (Raybiotech). Data were analysed with respect to T stage, nodal status, age and sex of the patient as well as time between collection of pre- and post-treatment serum. A significant decrease in the levels of the Th2 cytokines IL4, IL5, IL6 and IL10 and the Th1 cytokines IL2 and IL8 was observed between the pre- and post-treatment serum samples. IL13 and TNFα were significantly higher in early stage (T1/T2) tumours compared with late stage (T3/T4) and this trend was maintained for nodal involvement. IL4 was higher in node positive patients compared with node negative, whereas the converse was true for IL2; IL4 was also higher in younger patients compared with the older age group. These results suggest that removal of HNSCC tumours from patients results in reduced circulating Th2 cytokines without a concurrent increase in Th1 cytokines, indicative of a partial rebalance of the Th1/Th2 system following treatment. Furthermore the cytokine profile may be influenced by the size and nodal involvement of the tumour.</p></div>","PeriodicalId":89845,"journal":{"name":"Results in immunology","volume":"2 ","pages":"Pages 1-6"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinim.2011.12.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31985005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Results in immunologyPub Date : 2012-01-01Epub Date: 2012-01-08DOI: 10.1016/j.rinim.2012.01.001
Roland Fiskesund , Jun Su , Ivana Bulatovic , Max Vikström , Ulf de Faire , Johan Frostegård
{"title":"IgM phosphorylcholine antibodies inhibit cell death and constitute a strong protection marker for atherosclerosis development, particularly in combination with other auto-antibodies against modified LDL","authors":"Roland Fiskesund , Jun Su , Ivana Bulatovic , Max Vikström , Ulf de Faire , Johan Frostegård","doi":"10.1016/j.rinim.2012.01.001","DOIUrl":"10.1016/j.rinim.2012.01.001","url":null,"abstract":"<div><h3>Background</h3><p>We have reported that anti-phosphorylcholine (anti-PC) IgM is a protection marker for human cardiovascular disease (CVD) and atherosclerosis. We here investigate the anti-PC autoantibodies in a well-defined cohort with regard to idiotype, atherosclerosis progression and mechanisms for its protective action.</p></div><div><h3>Methods</h3><p>Serum levels and binding specificities of different anti-PC isotypes were determined in 226 hypertensive individuals enrolled in European Lacidipine Study on Atherosclerosis using ELISA. The mean of the maximum Intima-Media Thicknesses (IMT) in the far walls of common carotids and bifurcations was assessed at the time of inclusion, and four years afterwards. Apoptosis in immune cells was induced with lysophosphatidylcholine (LPC) and quantified using the MTT-assay.</p></div><div><h3>Results</h3><p>Anti-PC IgM, IgA and IgG1 (but not IgG2) was negatively associated with IMT-progression. Combining anti-PC IgM with data on antibodies against oxidized- and malondialdehyde-modified LDL further strengthened this association. At very high levels, anti-PC IgM exhibited a striking negative association with atherosclerosis progression (OR 0.05; CI 0.006–0.40). Analysis of serum samples taken four years apart in study participants affirmed the stability of anti-PC IgM titers over time. Examination of fine specificities revealed that the protective isotypes (IgM, IgA and IgG1) are of the Group I idiotype whereas the non-protective IgG2 subclass was Group II. Anti-PC IgM inhibited LPC-induced cell death of immune cells.</p></div><div><h3>Conclusion</h3><p>Group I anti-PC antibodies, particularly of the IgM class, are independent protection markers for atherosclerosis progression. One potential mechanism of action is inhibition of LPC-induced cell cytotoxicity.</p></div>","PeriodicalId":89845,"journal":{"name":"Results in immunology","volume":"2 ","pages":"Pages 13-18"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinim.2012.01.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31985007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Results in immunologyPub Date : 2012-01-01Epub Date: 2012-11-09DOI: 10.1016/j.rinim.2012.10.002
Subhajit Dasgupta , Jackie Eudaly
{"title":"Estrogen receptor-alpha mediates Toll-like receptor-2 agonist-induced monocyte chemoattractant protein-1 production in mesangial cells","authors":"Subhajit Dasgupta , Jackie Eudaly","doi":"10.1016/j.rinim.2012.10.002","DOIUrl":"10.1016/j.rinim.2012.10.002","url":null,"abstract":"<div><p>TLR2 agonists are well known for inducing NF-kB activation and inflammation, while estrogen receptor-alpha (ER-α) is a regulator of estrogen-mediated anti-inflammatory responses. In the present work, we determined the role of ER-α and phosphorylated ER-α in TLR2 agonist-induced MCP1 production in mesangial cells. We found that TLR2 agonists induced nuclear localization of phospho-ER-α (serine 118), and estrogen and TLR2 agonists both induced phosphorylation of ER-α at the serine 118 and 104/106 positions. Incubation of MRL/lpr mesangial cells with estrogen was found to attenuate TLR2 agonist-mediated MCP1 production. To determine the mode of action of ER-α/pER-α (serine-118), we used the ER-α inhibitor MPP and transfected mesangial cells with ER-α siRNA. ER-α inhibition was found to decrease MCP1 production in mesangial cells. Thus, ER-α/pER-α is an intermediate regulator for both TLR2-mediated MCP1 production during inflammation and estrogen-mediated anti-inflammatory signals in mesangial cells.</p></div>","PeriodicalId":89845,"journal":{"name":"Results in immunology","volume":"2 ","pages":"Pages 196-203"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinim.2012.10.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31982723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Results in immunologyPub Date : 2012-01-01Epub Date: 2012-11-20DOI: 10.1016/j.rinim.2012.11.001
Pedro C. Rodriguez , Roberto Torres-Moya , Gil Reyes , Claudino Molinero , Dinorah Prada , Ana M. Lopez , Isabel M. Hernandez , Maria V. Hernandez , Jose P. Martinez , Xochel Hernandez , Angel Casaco , Mayra Ramos , Yisel Avila , Yinet Barrese , Enrique Montero , Patricia Hernandez
{"title":"A clinical exploratory study with itolizumab, an anti-CD6 monoclonal antibody, in patients with rheumatoid arthritis","authors":"Pedro C. Rodriguez , Roberto Torres-Moya , Gil Reyes , Claudino Molinero , Dinorah Prada , Ana M. Lopez , Isabel M. Hernandez , Maria V. Hernandez , Jose P. Martinez , Xochel Hernandez , Angel Casaco , Mayra Ramos , Yisel Avila , Yinet Barrese , Enrique Montero , Patricia Hernandez","doi":"10.1016/j.rinim.2012.11.001","DOIUrl":"10.1016/j.rinim.2012.11.001","url":null,"abstract":"<div><p>T cells are involved in the pathogenesis of rheumatoid arthritis (RA). CD6 is a co-stimulatory molecule, predominantly expressed on lymphocytes, that has been linked to autoreactive responses. The purpose of this study was to evaluate the safety, immunogenicity and preliminary efficacy of itolizumab, a humanized anti-CD6 monoclonal antibody, in patients with active rheumatoid arthritis. Fifteen patients were enrolled in a phase I, open-label, dose-finding study. Five cohorts of patients received a weekly antibody monotherapy with a dose-range from 0.1 to 0.8 mg/kg. Itolizumab showed a good safety profile, with no severe or serious adverse events reported so far. No signs or symptoms associated with immunosuppression were observed in the study. Objective clinical responses were achieved in more than 80% of patients after treatment completion, and these responses tend to be sustained afterwards. This clinical study constitutes the first evidence of the safety and positive clinical effect of a monotherapy using an anti-CD6 antibody in patients with rheumatoid arthritis.</p></div>","PeriodicalId":89845,"journal":{"name":"Results in immunology","volume":"2 ","pages":"Pages 204-211"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinim.2012.11.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31982726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Results in immunologyPub Date : 2012-01-01Epub Date: 2012-05-15DOI: 10.1016/j.rinim.2012.05.001
Jeremy C. Parker , Surendran Thavagnanam , Grzegorz Skibinski , Michael McBrien , Liam G. Heaney , Michael D. Shields
{"title":"IL-31 does not induce normal human ciliated epithelial cells to differentiate into a phenotype consistent with the pathophysiology of asthma","authors":"Jeremy C. Parker , Surendran Thavagnanam , Grzegorz Skibinski , Michael McBrien , Liam G. Heaney , Michael D. Shields","doi":"10.1016/j.rinim.2012.05.001","DOIUrl":"10.1016/j.rinim.2012.05.001","url":null,"abstract":"<div><h3>Background</h3><p>IL-31 is a novel cytokine that has been implicated in allergic diseases such as atopic dermatitis and more recently asthma. While IL-31 has been well studied in skin conditions such as atopic dermatitis, little is known about the role IL-31 plays in asthma and specifically the differentiation process of the bronchial epithelium, which is central to the pathogenesis of allergic asthma.</p></div><div><h3>Methods</h3><p>We examined the effects of IL-13 (20<!--> <!-->ng/ml), IL-31 (20<!--> <!-->ng/ml) and an IL-13/IL-31 combination stimulation (20<!--> <!-->ng/ml each) on the <em>in vitro</em> mucociliary differentiation of paediatric bronchial epithelial cells (PBECs) from healthy patients (<em>n</em>=6). IL-31 receptor (IL-31-RA) expression, markers of differentiation (goblet and ciliated cells), transepithelial electrical resistance (TEER), quantification of goblet and ciliated cells, real time PCR for MUC5AC, ELISA for VEGF, EGF and MCP-1 (CCL-2) and ELISA for MUC5AC were assessed.</p></div><div><h3>Results</h3><p>We found that well-differentiated PBECs expressed IL-31-RA however it's expression did not increase upon stimulation with IL-31 or either of the other treatments. TEER indicated good formation of tight junctions which was found to be similar across all treatment groups (<em>p</em>=0.9). We found that IL-13 alone significantly reduced the number of ciliated cells compared with unstimulated (IL-13 stimuation: mean=4.8% (SD=2.5); unstimulated: mean=15.9%, (SD=7.4), <em>p</em><0.01). IL-31 stimulation alone had no effect on ciliated cells whereas the IL-13/IL-31 combination stimulation significantly reduced the number of ciliated cells compared with control (IL-13/IL-31 combination: mean=5.1% (SD=4.6); unstimulated: mean=15.9%, (SD=7.4), <em>p</em><0.01). We did not find that the combination of IL-13 and IL-31 had any additional effects to that of IL-13 alone. MUC5AC mRNA and secreted mucin was found in similar levels between unstimulated and all treatments, however IL-13 increased levels of MUC5AC mRNA by a factor of 2.84, albeit not significantly, compared with unstimulated cultures (IL-13 stimulation: mean=2.84 (SD=3.79); unstimulated: mean=1.0).</p></div><div><h3>Conclusions</h3><p>IL-31RA receptor is present on well-differentiated paediatric bronchial epithelial cells. IL-31 does not exhibit any detrimental effects on mucociliary differentiation. IL-31 does not appear to have a synergistic effect when combined in culture with IL-13, in the differentiation process.</p></div>","PeriodicalId":89845,"journal":{"name":"Results in immunology","volume":"2 ","pages":"Pages 104-111"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinim.2012.05.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31984448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}