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      CXCL-16, IL-17, and bone morphogenetic protein 2 (BMP-2) are associated with overweight and obesity conditions in middle-aged and elderly women

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          Abstract

          Background

          The current concept of overweight/obesity is most likely related to a combination of increased caloric intake and decreased energy expenditure. Widespread inflammation, associated with both conditions, appears to contribute to the development of some obesity-related comorbidities. Interventions that directly or indirectly target individuals at high risk of developing obesity have been largely proposed because of the increasing number of overweight/obese cases worldwide. The aim of the present study was to assess CXCL16, IL-17, and BMP-2 plasma factors in middle-aged and elderly women and relate them to an overweight or obese status. In total, 117 women were selected and grouped as eutrophic, overweight, and obese, according to anthropometric parameters. Analyses of anthropometric and circulating biochemical parameters were followed by plasma immunoassays for CXCL-16, IL-17, and BMP-2.

          Results

          Plasma mediators increased in all overweight and obese individuals, with the exception of BMP-2 in the elderly group, whereas CXCL16 levels were shown to differentiate overweight and obese individuals. Overweight and/or obese middle-aged and elderly individuals presented with high LDL, triglycerides, and glycemia levels. Anthropometric parameters indicating increased-cardiovascular risk were positively correlated with CXCL-16, BMP-2, and IL-17 levels in overweight and obese middle-aged and elderly individuals.

          Conclusion

          This study provides evidence that CXCL-16, IL-17, and BMP-2 are potential plasma indicators of inflammatory status in middle-aged and elderly women; therefore, further investigation of obesity-related comorbidities is recommended. CXCL16, in particular, could be a potential marker for middle-aged and elderly individuals transitioning from eutrophic to overweight body types, which represents an asymptomatic and dangerous condition.

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          The immune system and aging: a review.

          Camil Castelo-Branco, Iris Soveral (2014)
          Abstract The concept of immunosenescence reflects age-related changes in immune responses, both cellular and serological, affecting the process of generating specific responses to foreign and self-antigens. The decline of the immune system with age is reflected in the increased susceptibility to infectious diseases, poorer response to vaccination, increased prevalence of cancer, autoimmune and other chronic diseases. Both innate and adaptive immune responses are affected by the aging process; however, the adaptive response seems to be more affected by the age-related changes in the immune system. Additionally, aged individuals tend to present a chronic low-grade inflammatory state that has been implicated in the pathogenesis of many age-related diseases (atherosclerosis, Alzheimer's disease, osteoporosis and diabetes). However, some individuals arrive to advanced ages without any major health problems, referred to as healthy aging. The immune system dysfunction seems to be somehow mitigated in this population, probably due to genetic and environmental factors yet to be described. In this review, an attempt is made to summarize the current knowledge on how the immune system is affected by the aging process.
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            CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity.

            Bernhard Ludvik, F. W. Kiefer, Gerd Silberhumer … (2008)
            Obesity is associated with a low-grade inflammation, insulin resistance, and macrophage infiltration of adipose tissue. The role of CC chemokines and their respective receptors in human adipose tissue inflammation remains to be determined. sc and visceral adipose tissue of obese patients (body mass index 53.1 +/- 11.3 kg/m(2)) compared with lean controls (body mass index 25.9 +/- 3.8 kg/m(2)) was analyzed for alterations in inflammatory gene expression. Macrophage infiltration was increased in sc and visceral adipose tissue of obese patients as determined by increased mRNA expression of a macrophage-specific marker (CD68) and by elevated macrophage infiltration. Gene expression of CC chemokines involved in monocyte chemotaxis (CCL2, CCL3, CCL5, CCL7, CCL8, and CCL11) and their receptors (CCR1, CCR2, CCR3, and CCR5) was higher in sc and visceral adipose tissue of obese patients. Serum concentrations of the inflammatory marker IL-6 and C-reactive protein were elevated in obese patients compared with lean controls. Obese patients revealed increased insulin resistance as assessed by the homeostasis model assessment of insulin resistance index and reduced plasma adiponectin concentrations. Adipose tissue expression of many CC chemokines and their receptors in the obese group positively correlated with CD68 expression. Up-regulation of the CC chemokines and their respective receptors in adipose tissue occurs in human obesity and is associated with increased systemic inflammation.
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              Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells.

              Bonnie B Blomberg, Robert Schwartz, Ana Landin … (2008)
              Elderly humans have compromised humoral and cellular immune responses, which lead to reduced protection to infectious agents and to vaccines. Currently, available vaccines suboptimally protect the elderly population. The capacity to class switch the Ig H chain is critical to the effectiveness of humoral immune responses in mice and humans. We have previously shown in mice that the E2A-encoded transcription factor E47, which regulates many B cell functions, is down-regulated in old splenic B cells. This leads to a reduction in the activation-induced cytidine deaminase (AID), which is known to induce class switch recombination and Ig somatic hypermutation. The old activated murine B cells also have less AID and less switched Abs. We have extended our study here to investigate whether aging also affects Ab production and E47 and AID expression in B cells isolated from the peripheral blood of human subjects (18-86 years). Our results obtained with activated CD19(+) B cells show that the expression of E47, AID, and Iggamma1 circle transcripts progressively decrease with age. We also show an age-related decline in the percentage of switch memory B cells (IgG(+)/IgA(+)), an increase in that of naive B cells (IgG(-)/IgA(-)/CD27(-)) for most individuals, and no decrease in that of IgM memory cells in peripheral blood, consistent with our data on the decrease seen in class switch recombination in vitro. Our results provide a possible molecular mechanism for a B cell intrinsic defect in the humoral immune response with aging and suggest avenues for improvement of vaccine response in elderly humans.
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                Author and article information

                Contributors
                Silvana Mara Turbino Luz Ribeiro: silvanamara@uai.com.br
                Laís Roquete Lopes: laisroquete@hotmail.com
                Guilherme de Paula Costa: gpcostabio@gmail.com
                Vivian Paulino Figueiredo: vivian_figueiredo@yahoo.com.br
                Deena Shrestha: deenabajra@gmail.com
                Aline Priscila Batista: alinepriop@yahoo.com.br
                Roney Luiz de Carvalho Nicolato: nicolato@ef.ufop.br
                Fernando Luiz Pereira de Oliveira: fernandoluizest@gmail.com
                Juliana Assis Silva Gomes: estanislau.juliana@gmail.com
                Andre Talvani:
                ORCID: http://orcid.org/0000-0002-6685-6229
                55 31 3559 1690 , talvani@nupeb.ufop.br
                Journal
                Journal ID (nlm-ta): Immun Ageing
                Journal ID (iso-abbrev): Immun Ageing
                Title: Immunity & Ageing : I & A
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1742-4933
                Publication date (Electronic): 11 March 2017
                Publication date PMC-release: 11 March 2017
                Publication date Collection: 2017
                Volume: 14
                Electronic Location Identifier: 6
                Affiliations
                [1 ]ISNI 0000 0004 0488 4317, GRID grid.411213.4, Department of Biological Sciences, , Federal University of Ouro Preto, ; Ouro Preto, Minas Gerais Brazil
                [2 ]ISNI 0000 0004 0488 4317, GRID grid.411213.4, Post-graduation Program in Biological Sciences/NUPEB, , Federal University of Ouro Preto, ; Ouro Preto, Minas Gerais Brazil
                [3 ]ISNI 0000 0004 0488 4317, GRID grid.411213.4, Post-graduation Program in Health and Nutrition, , Federal University of Ouro Preto, ; Ouro Preto, Minas Gerais Brazil
                [4 ]ISNI 0000 0004 0488 4317, GRID grid.411213.4, Post-graduation in Ecology of Tropical Biomas, , Federal University of Ouro Preto, ; Ouro Preto, Minas Gerais Brazil
                [5 ]ISNI 0000 0004 0488 4317, GRID grid.411213.4, Clinical Analyses Laboratory of the Pharmacy School, , Federal University of Ouro Preto, ; Ouro Preto, Minas Gerais Brazil
                [6 ]ISNI 0000 0004 0488 4317, GRID grid.411213.4, Department of Statistics, , Federal University of Ouro Preto, ; Ouro Preto, Minas Gerais Brazil
                [7 ]ISNI 0000 0004 0488 4317, GRID grid.411213.4, Laboratory of the Immunobiology of Inflammation, , Federal University of Ouro Preto, ; Ouro Preto, Minas Gerais Brazil
                [8 ]ISNI 0000 0001 2181 4888, GRID grid.8430.f, Department of Morphology, , Federal University of Minas Gerais, ; Belo Horizonte, Minas Gerais Brazil
                Author information
                http://orcid.org/0000-0002-6685-6229
                Article
                Publisher ID: 89
                DOI: 10.1186/s12979-017-0089-0
                PMC ID: 5346187
                PubMed ID: 28293269
                SO-VID: 71f548f7-166e-4846-b697-1be348639a65
                Copyright © © The Author(s). 2017
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 19 September 2016
                Date accepted : 27 February 2017
                Funding
                Funded by: CNPQ
                Award ID: Bolsa de Produtividade # 305457/2013-6
                Award Recipient :
                Funded by: UFOP
                Award ID: Auxílio-Pesquisador Processo # 23109.003209/201698
                Award Recipient :
                Funded by: FAPEMIG
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2017

                ScienceOpen disciplines: Immunology
                Keywords: inflammation,elderly,overweight,obesity,cxcl-16,bmp-2,il-17
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: inflammation, elderly, overweight, obesity, cxcl-16, bmp-2, il-17

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