What are the living conditions and health status of those who don't report their migration status? a population-based study in Chile

BACKGROUND: Undocumented immigrants are likely to be missing from population databases, making it impossible to identify an accurate sampling frame in migration research. No population-based data has been collected in Chile regarding the living conditions and health status of undocumented immigrants. However, the CASEN survey (Caracterizacion Socio- Economica Nacional) asked about migration status in Chile for the first time in 2006 and provides an opportunity to set the base for future analysis of available migration data. We explored the living conditions and health of self-reported immigrants and respondents who preferred not to report their migration status in this survey. METHODS: Cross-sectional secondary analysis of CASEN survey in Chile in 2006. Outcomes: any disability, illness/accident, hospitalization/surgery, cancer/chronic condition (all binary variables); and the number of medical/emergency attentions received (count variables). Covariates: Demographics (age, sex, marital status, urban/rural, ethnicity), socioeconomic status (education level, employment status and household income), and material standard of living (overcrowding, sanitation, housing quality). Weighted regression models were estimated for each health outcome, crude and adjusted by sets of covariates, in STATA 10.0. RESULTS: About 1% of the total sample reported being immigrants and 0.7% preferred not to report their migration status (Migration Status - Missing Values; MS-MV). The MS-MV lived in more deprived conditions and reported a higher rate of health problems than immigrants. Some gender differences were observed by health status among immigrants and the MS-MV but they were not statistically significant. Regressions indicated that age, sex, SES and material factors consistently affected MS-MVs’ chance of presenting poor health and these patterns were different to those found among immigrants. Great heterogeneity in both the MS-MV and the immigrants, as indicated by wide confidence intervals, prevented the identification of other significantly associated covariates. CONCLUSION: This is the first study to look at the living conditions and health of those that preferred not to respond their migration status in Chile. Respondents that do not report their migration status are vulnerable to poor health and may represent undocumented immigrants. Surveys that fail to identify these people are likely to misrepresent the experiences of immigrants and further quantitative and qualitative research is urgently required

A meta-analysis reveals the commonalities and differences in Arabidopsis thaliana response to different viral pathogens

Understanding the mechanisms by which plants trigger host defenses in response to viruses has been a challenging problem owing to the multiplicity of factors and complexity of interactions involved. The advent of genomic techniques, however, has opened the possibility to grasp a global picture of the interaction. Here, we used Arabidopsis thaliana to identify and compare genes that are differentially regulated upon infection with seven distinct (+)ssRNA and one ssDNA plant viruses. In the first approach, we established lists of genes differentially affected by each virus and compared their involvement in biological functions and metabolic processes. We found that phylogenetically related viruses significantly alter the expression of similar genes and that viruses naturally infecting Brassicaceae display a greater overlap in the plant response. In the second approach, virus-regulated genes were contextualized using models of transcriptional and protein-protein interaction networks of A. thaliana. Our results confirm that host cells undergo significant reprogramming of their transcriptome during infection, which is possibly a central requirement for the mounting of host defenses. We uncovered a general mode of action in which perturbations preferentially affect genes that are highly connected, central and organized in modules. © 2012 Rodrigo et al.This work was supported by the Spanish Ministerio de Ciencia e Innovacion (MICINN) grants BFU2009-06993 (S. F. E.) and BIO2006-13107 (C. L.) and by Generalitat Valenciana grant PROMETEO2010/016 (S. F. E.). G. R. is supported by a graduate fellowship from the Generalitat Valenciana (BFPI2007-160) and J.C. by a contract from MICINN grant TIN2006-12860. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Rodrigo Tarrega, G.; Carrera Montesinos, J.; Ruiz-Ferrer, V.; Del Toro, F.; Llave, C.; Voinnet, O.; Elena Fito, SF. (2012). A meta-analysis reveals the commonalities and differences in Arabidopsis thaliana response to different viral pathogens. PLoS ONE. 7(7):40526-40526. https://doi.org/10.1371/journal.pone.0040526S405264052677Peng, X., Chan, E. Y., Li, Y., Diamond, D. L., Korth, M. J., & Katze, M. G. (2009). Virus–host interactions: from systems biology to translational research. Current Opinion in Microbiology, 12(4), 432-438. doi:10.1016/j.mib.2009.06.003Dodds, P. N., & Rathjen, J. P. (2010). Plant immunity: towards an integrated view of plant–pathogen interactions. Nature Reviews Genetics, 11(8), 539-548. doi:10.1038/nrg2812Maule, A., Leh, V., & Lederer, C. (2002). The dialogue between viruses and hosts in compatible interactions. Current Opinion in Plant Biology, 5(4), 279-284. doi:10.1016/s1369-5266(02)00272-8Whitham, S. A., Quan, S., Chang, H.-S., Cooper, B., Estes, B., Zhu, T., … Hou, Y.-M. (2003). Diverse RNA viruses elicit the expression of common sets of genes in susceptibleArabidopsis thalianaplants. The Plant Journal, 33(2), 271-283. doi:10.1046/j.1365-313x.2003.01625.xBailer, S., & Haas, J. (2009). Connecting viral with cellular interactomes. Current Opinion in Microbiology, 12(4), 453-459. doi:10.1016/j.mib.2009.06.004Whitham, S. A., Yang, C., & Goodin, M. M. (2006). Global Impact: Elucidating Plant Responses to Viral Infection. Molecular Plant-Microbe Interactions, 19(11), 1207-1215. doi:10.1094/mpmi-19-1207MacPherson, J. I., Dickerson, J. E., Pinney, J. W., & Robertson, D. L. (2010). Patterns of HIV-1 Protein Interaction Identify Perturbed Host-Cellular Subsystems. PLoS Computational Biology, 6(7), e1000863. doi:10.1371/journal.pcbi.1000863Jenner, R. G., & Young, R. A. (2005). Insights into host responses against pathogens from transcriptional profiling. Nature Reviews Microbiology, 3(4), 281-294. doi:10.1038/nrmicro1126Andeweg, A. C., Haagmans, B. L., & Osterhaus, A. D. (2008). Virogenomics: the virus–host interaction revisited. Current Opinion in Microbiology, 11(5), 461-466. doi:10.1016/j.mib.2008.09.010Elena, S. F., Carrera, J., & Rodrigo, G. (2011). A systems biology approach to the evolution of plant–virus interactions. Current Opinion in Plant Biology, 14(4), 372-377. doi:10.1016/j.pbi.2011.03.013Tan, S.-L., Ganji, G., Paeper, B., Proll, S., & Katze, M. G. (2007). Systems biology and the host response to viral infection. Nature Biotechnology, 25(12), 1383-1389. doi:10.1038/nbt1207-1383De la Fuente, A. (2010). From ‘differential expression’ to ‘differential networking’ – identification of dysfunctional regulatory networks in diseases. Trends in Genetics, 26(7), 326-333. doi:10.1016/j.tig.2010.05.001Albert, R. (2005). Scale-free networks in cell biology. Journal of Cell Science, 118(21), 4947-4957. doi:10.1242/jcs.02714Yu, H., Braun, P., Yildirim, M. A., Lemmens, I., Venkatesan, K., Sahalie, J., … Vidal, M. (2008). High-Quality Binary Protein Interaction Map of the Yeast Interactome Network. Science, 322(5898), 104-110. doi:10.1126/science.1158684Barabási, A.-L., & Oltvai, Z. N. (2004). Network biology: understanding the cell’s functional organization. Nature Reviews Genetics, 5(2), 101-113. doi:10.1038/nrg1272Albert, R., Jeong, H., & Barabási, A.-L. (2000). Error and attack tolerance of complex networks. Nature, 406(6794), 378-382. doi:10.1038/35019019Mukhtar, M. S., Carvunis, A.-R., Dreze, M., Epple, P., Steinbrenner, J., … Moore, J. (2011). Independently Evolved Virulence Effectors Converge onto Hubs in a Plant Immune System Network. Science, 333(6042), 596-601. doi:10.1126/science.1203659Calderwood, M. A., Venkatesan, K., Xing, L., Chase, M. R., Vazquez, A., Holthaus, A. M., … Johannsen, E. (2007). Epstein-Barr virus and virus human protein interaction maps. Proceedings of the National Academy of Sciences, 104(18), 7606-7611. doi:10.1073/pnas.0702332104De Chassey, B., Navratil, V., Tafforeau, L., Hiet, M. S., Aublin‐Gex, A., Agaugué, S., … Lotteau, V. (2008). Hepatitis C virus infection protein network. Molecular Systems Biology, 4(1), 230. doi:10.1038/msb.2008.66Shapira, S. D., Gat-Viks, I., Shum, B. O. V., Dricot, A., de Grace, M. M., Wu, L., … Hacohen, N. (2009). A Physical and Regulatory Map of Host-Influenza Interactions Reveals Pathways in H1N1 Infection. Cell, 139(7), 1255-1267. doi:10.1016/j.cell.2009.12.018Dyer, M. D., Murali, T. M., & Sobral, B. W. (2008). The Landscape of Human Proteins Interacting with Viruses and Other Pathogens. PLoS Pathogens, 4(2), e32. doi:10.1371/journal.ppat.0040032Golem, S., & Culver, J. N. (2003). Tobacco mosaic virusInduced Alterations in the Gene Expression Profile ofArabidopsis thaliana. Molecular Plant-Microbe Interactions, 16(8), 681-688. doi:10.1094/mpmi.2003.16.8.681Espinoza, C., Medina, C., Somerville, S., & Arce-Johnson, P. (2007). Senescence-associated genes induced during compatible viral interactions with grapevine and Arabidopsis. Journal of Experimental Botany, 58(12), 3197-3212. doi:10.1093/jxb/erm165Yang, C., Guo, R., Jie, F., Nettleton, D., Peng, J., Carr, T., … Whitham, S. A. (2007). Spatial Analysis ofArabidopsis thalianaGene Expression in Response toTurnip mosaic virusInfection. Molecular Plant-Microbe Interactions, 20(4), 358-370. doi:10.1094/mpmi-20-4-0358Agudelo-Romero, P., Carbonell, P., de la Iglesia, F., Carrera, J., Rodrigo, G., Jaramillo, A., … Elena, S. F. (2008). Changes in the gene expression profile of Arabidopsis thaliana after infection with Tobacco etch virus. Virology Journal, 5(1), 92. doi:10.1186/1743-422x-5-92Agudelo-Romero, P., Carbonell, P., Perez-Amador, M. A., & Elena, S. F. (2008). Virus Adaptation by Manipulation of Host’s Gene Expression. PLoS ONE, 3(6), e2397. doi:10.1371/journal.pone.0002397Ascencio-Ibáñez, J. T., Sozzani, R., Lee, T.-J., Chu, T.-M., Wolfinger, R. D., Cella, R., & Hanley-Bowdoin, L. (2008). Global Analysis of Arabidopsis Gene Expression Uncovers a Complex Array of Changes Impacting Pathogen Response and Cell Cycle during Geminivirus Infection. Plant Physiology, 148(1), 436-454. doi:10.1104/pp.108.121038Babu, M., Griffiths, J. S., Huang, T.-S., & Wang, A. (2008). Altered gene expression changes in Arabidopsis leaf tissues and protoplasts in response to Plum pox virus infection. BMC Genomics, 9(1), 325. doi:10.1186/1471-2164-9-325De Vienne, D. M., Giraud, T., & Martin, O. C. (2007). A congruence index for testing topological similarity between trees. Bioinformatics, 23(23), 3119-3124. doi:10.1093/bioinformatics/btm500Wise, R. P., Moscou, M. J., Bogdanove, A. J., & Whitham, S. A. (2007). Transcript Profiling in Host–Pathogen Interactions. Annual Review of Phytopathology, 45(1), 329-369. doi:10.1146/annurev.phyto.45.011107.143944Handford, M. G., & Carr, J. P. (2007). A defect in carbohydrate metabolism ameliorates symptom severity in virus-infected Arabidopsis thaliana. Journal of General Virology, 88(1), 337-341. doi:10.1099/vir.0.82376-0Hou, B., Lim, E.-K., Higgins, G. S., & Bowles, D. J. (2004). N-Glucosylation of Cytokinins by Glycosyltransferases ofArabidopsis thaliana. Journal of Biological Chemistry, 279(46), 47822-47832. doi:10.1074/jbc.m409569200Schwender, J., Goffman, F., Ohlrogge, J. B., & Shachar-Hill, Y. (2004). Rubisco without the Calvin cycle improves the carbon efficiency of developing green seeds. Nature, 432(7018), 779-782. doi:10.1038/nature03145Pagán, I., Alonso-Blanco, C., & García-Arenal, F. (2008). Host Responses in Life-History Traits and Tolerance to Virus Infection in Arabidopsis thaliana. PLoS Pathogens, 4(8), e1000124. doi:10.1371/journal.ppat.1000124Carrera, J., Rodrigo, G., Jaramillo, A., & Elena, S. F. (2009). Reverse-engineering the Arabidopsis thaliana transcriptional network under changing environmental conditions. Genome Biology, 10(9), R96. doi:10.1186/gb-2009-10-9-r96Geisler-Lee, J., O’Toole, N., Ammar, R., Provart, N. J., Millar, A. H., & Geisler, M. (2007). A Predicted Interactome for Arabidopsis. Plant Physiology, 145(2), 317-329. doi:10.1104/pp.107.103465Ma, S., Gong, Q., & Bohnert, H. J. (2007). An Arabidopsis gene network based on the graphical Gaussian model. Genome Research, 17(11), 1614-1625. doi:10.1101/gr.6911207Yamada, T., & Bork, P. (2009). Evolution of biomolecular networks — lessons from metabolic and protein interactions. Nature Reviews Molecular Cell Biology, 10(11), 791-803. doi:10.1038/nrm2787Humphries, M. D., & Gurney, K. (2008). Network ‘Small-World-Ness’: A Quantitative Method for Determining Canonical Network Equivalence. PLoS ONE, 3(4), e0002051. doi:10.1371/journal.pone.0002051Stumpf, M. P. H., & Ingram, P. J. (2005). Probability models for degree distributions of protein interaction networks. Europhysics Letters (EPL), 71(1), 152-158. doi:10.1209/epl/i2004-10531-8Khanin, R., & Wit, E. (2006). How Scale-Free Are Biological Networks. Journal of Computational Biology, 13(3), 810-818. doi:10.1089/cmb.2006.13.810Daudin, J.-J., Picard, F., & Robin, S. (2007). A mixture model for random graphs. Statistics and Computing, 18(2), 173-183. doi:10.1007/s11222-007-9046-7Uetz, P. (2006). Herpesviral Protein Networks and Their Interaction with the Human Proteome. Science, 311(5758), 239-242. doi:10.1126/science.1116804Choi, I.-R., Stenger, D. C., & French, R. (2000). Multiple Interactions among Proteins Encoded by the Mite-Transmitted Wheat Streak Mosaic Tritimovirus. Virology, 267(2), 185-198. doi:10.1006/viro.1999.0117Guo, D., Saarma, M., Rajamäki, M.-L., & Valkonen, J. P. T. (2001). Towards a protein interaction map of potyviruses: protein interaction matrixes of two potyviruses based on the yeast two-hybrid system. Journal of General Virology, 82(4), 935-939. doi:10.1099/0022-1317-82-4-935Lin, L., Shi, Y., Luo, Z., Lu, Y., Zheng, H., Yan, F., … Wu, Y. (2009). Protein–protein interactions in two potyviruses using the yeast two-hybrid system. Virus Research, 142(1-2), 36-40. doi:10.1016/j.virusres.2009.01.006Shen, W., Wang, M., Yan, P., Gao, L., & Zhou, P. (2010). Protein interaction matrix of Papaya ringspot virus type P based on a yeast two-hybrid system. Acta Virologica, 54(1), 49-54. doi:10.4149/av_2010_01_49Redner, S. (2008). Teasing out the missing links. Nature, 453(7191), 47-48. doi:10.1038/453047aIrizarry, R. A. (2003). Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics, 4(2), 249-264. doi:10.1093/biostatistics/4.2.249Smyth, G. K. (2004). Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments. Statistical Applications in Genetics and Molecular Biology, 3(1), 1-25. doi:10.2202/1544-6115.1027Allemeersch, J., Durinck, S., Vanderhaeghen, R., Alard, P., Maes, R., Seeuws, K., … Kuiper, M. T. R. (2005). Benchmarking the CATMA Microarray. A Novel Tool forArabidopsis Transcriptome Analysis. Plant Physiology, 137(2), 588-601. doi:10.1104/pp.104.051300Cleveland, W. S. (1979). Robust Locally Weighted Regression and Smoothing Scatterplots. Journal of the American Statistical Association, 74(368), 829-836. doi:10.1080/01621459.1979.10481038Tarraga, J., Medina, I., Carbonell, J., Huerta-Cepas, J., Minguez, P., Alloza, E., … Dopazo, J. (2008). GEPAS, a web-based tool for microarray data analysis and interpretation. Nucleic Acids Research, 36(Web Server), W308-W314. doi:10.1093/nar/gkn303Al-Shahrour, F., Minguez, P., Vaquerizas, J. M., Conde, L., & Dopazo, J. (2005). BABELOMICS: a suite of web tools for functional annotation and analysis of groups of genes in high-throughput experiments. Nucleic Acids Research, 33(Web Server), W460-W464. doi:10.1093/nar/gki456Al-Shahrour, F., Minguez, P., Tárraga, J., Medina, I., Alloza, E., Montaner, D., & Dopazo, J. (2007). FatiGO +: a functional profiling tool for genomic data. Integration of functional annotation, regulatory motifs and interaction data with microarray experiments. Nucleic Acids Research, 35(suppl_2), W91-W96. doi:10.1093/nar/gkm260Mueller, L. A., Zhang, P., & Rhee, S. Y. (2003). AraCyc: A Biochemical Pathway Database for Arabidopsis. Plant Physiology, 132(2), 453-460. doi:10.1104/pp.102.017236Navratil, V., de Chassey, B., Combe, C., & Lotteau, V. (2011). When the human viral infectome and diseasome networks collide: towards a systems biology platform for the aetiology of human diseases. BMC Systems Biology, 5(1), 13. doi:10.1186/1752-0509-5-13Shannon, C. E. (1948). A Mathematical Theory of Communication. Bell System Technical Journal, 27(3), 379-423. doi:10.1002/j.1538-7305.1948.tb01338.

Disappearance and appearance of an indigestible marker in feces from growing pigs as affected by previous- and current-diet composition

Abstract Background Indigestible markers are commonly utilized in digestion studies, but the complete disappearance or maximum appearance of a marker in feces can be affected by diet composition, feed intake, or an animal’s BW. The objectives of this study were to determine the impact of previous (Phase 1, P1) and current- (Phase 2, P2) diet composition on marker disappearance (Cr) and appearance (Ti) in pigs fed 3 diets differing in NDF content. Results When pigs were maintained on the 25.1, 72.5, and 125.0 g/kg NDF diets, it took 5.1, 4.1, and 2.5 d, respectively, for Cr levels to decrease below the limit of quantitation; or 4.6, 3.7, or 2.8 d, respectively, for Ti to be maximized. These effects were not, however, independent of the previous diet as indicated by the interaction between P1 and P2 diets on fecal marker concentrations (P < 0.01). When dietary NDF increased from P1 to P2, it took less time for fecal Cr to decrease or fecal Ti to be maximized (an average of 2.5 d), than if NDF decreased from P1 to P2 where it took longer for fecal Cr to decrease or fecal Ti to be maximized (an average of 3.4 d). Conclusions Because of the wide range in excretion times reported in the literature and improved laboratory methods for elemental detection, the data suggests that caution must be taken in considering dietary fiber concentrations of the past and currently fed diets so that no previous dietary marker addition remains in the digestive tract or feces such that a small amount of maker is present to confound subsequent experimental results, and that marker concentration have stabilized when these samples are collected

Tegumentary leishmaniasis and coinfections other than HIV

<div><p>Background</p><p>Tegumentary leishmaniasis (TL) is a disease of skin and/or mucosal tissues caused by <i>Leishmania</i> parasites. TL patients may concurrently carry other pathogens, which may influence the clinical outcome of TL.</p><p>Methodology and principal findings</p><p>This review focuses on the frequency of TL coinfections in human populations, interactions between <i>Leishmania</i> and other pathogens in animal models and human subjects, and implications of TL coinfections for clinical practice. For the purpose of this review, TL is defined as all forms of cutaneous (localised, disseminated, or diffuse) and mucocutaneous leishmaniasis. Human immunodeficiency virus (HIV) coinfection, superinfection with skin bacteria, and skin manifestations of visceral leishmaniasis are not included. We searched MEDLINE and other databases and included 73 records: 21 experimental studies in animals and 52 studies about human subjects (mainly cross-sectional and case studies). Several reports describe the frequency of <i>Trypanosoma cruzi</i> coinfection in TL patients in Argentina (about 41%) and the frequency of helminthiasis in TL patients in Brazil (15% to 88%). Different hypotheses have been explored about mechanisms of interaction between different microorganisms, but no clear answers emerge. Such interactions may involve innate immunity coupled with regulatory networks that affect quality and quantity of acquired immune responses. Diagnostic problems may occur when concurrent infections cause similar lesions (e.g., TL and leprosy), when different pathogens are present in the same lesions (e.g., <i>Leishmania</i> and <i>Sporothrix schenckii</i>), or when similarities between phylogenetically close pathogens affect accuracy of diagnostic tests (e.g., serology for leishmaniasis and Chagas disease). Some coinfections (e.g., helminthiasis) appear to reduce the effectiveness of antileishmanial treatment, and drug combinations may cause cumulative adverse effects.</p><p>Conclusions and significance</p><p>In patients with TL, coinfection is frequent, it can lead to diagnostic errors and delays, and it can influence the effectiveness and safety of treatment. More research is needed to unravel how coinfections interfere with the pathogenesis of TL.</p></div

External validation of prognostic models to predict stillbirth using the International Prediction of Pregnancy Complications (IPPIC) Network database: an individual participant data meta-analysis

Objective Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. Methods MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit. Results Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes. Conclusions The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. (c) 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.Peer reviewe

Antagonism of cannabinoid receptor 2 pathway suppresses IL-6-induced immunoglobulin IgM secretion

Background: Cannabinoid receptor 2 (CB2) is expressed predominantly in the immune system, particularly in plasma cells, raising the possibility that targeting the CB2 pathway could yield an immunomodulatory effect. Although the role of CB2 in mediating immunoglobulin class switching has been reported, the effects of targeting the CB2 pathway on immunoglobulin secretion per se remain unclear. Methods: Human B cell line SKW 6.4, which is capable of differentiating into IgM-secreting cells once treated with human IL-6, was employed as the cell model. SKW 6.4 cells were incubated for 4 days with CB2 ligands plus IL-6 (100 U/ml). The amount of secreted IgM was determined by an ELISA. Cell proliferation was determined by the 3H-Thymidine incorporation assay. Signal molecules involved in the modulation of IgM secretion were examined by real-time RT-PCR and Western blot analyses or by using their specific inhibitors. Results: We demonstrated that CB2 inverse agonists SR144528 and AM630, but not CB2 agonist HU308 or CB1 antagonist SR141716, effectively inhibited IL-6-induced secretion of soluble IgM without affecting cell proliferation as measured by thymidine uptake. SR144528 alone had no effects on the basal levels of IgM in the resting cells. These effects were receptor mediated, as pretreatment with CB2 agonist abrogated SR144528-mediated inhibition of IL-6 stimulated IgM secretion. Transcription factors relevant to B cell differentiation, Bcl-6 and PAX5, as well as the protein kinase STAT3 pathway were involved in the inhibition of IL-6-induced IgM by SR144528. Conclusions: These results uncover a novel function of CB2 antagonists and suggest that CB2 ligands may be potential modulators of immunoglobulin secretion