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Valentina Bruno, Judit Svensson-Arvelund, Marie Rubér, Göran Berg, Emilio Piccione, Maria C Jenmalm, Jan Ernerudh
Low molecular weight heparin (LMWH) is widely used in recurrent miscarriage treatment. The anti-coagulant effects are established, while immunological effects are not fully known. Our aim was to assess LMWH effects on activation and polarization of central regulatory immune cells from healthy women, and on placenta tissues from women undergoing elective abortions. Isolated blood monocytes and T helper (Th) cells under different activation and polarizing conditions were cultured with or without LMWH. Flow cytometry showed that LMWH exposure induced increased expression of HLA-DR and CD206 in macrophages...
March 8, 2018: Scientific Reports
Shinya Yamamoto, Kazuhiko Matsuo, Daisuke Nagakubo, Shintaro Higashiyama, Keiji Nishiwaki, Naoki Oiso, Akira Kawada, Osamu Yoshie, Takashi Nakayama
CCR4 is a major chemokine receptor expressed by Treg cells that downregulate immune responses. Here, we investigated the role of CCR4-mediated Treg cell recruitment in antigen-specific immune responses. CCR4-deficient mice immunized intramuscularly with ovalbumin (OVA) showed enhanced OVA-specific IgG responses. Furthermore, intramuscular administration of OVA induced the expression of MDC/CCL22, a ligand for CCR4, in macrophages of the muscle tissues, and enhanced the recruitment of CCR4+ Treg cells in wild-type mice, whereas this recruitment of Treg cells was severely impaired in CCR4-deficient mice...
February 8, 2018: Journal of Pharmacological Sciences
Kazuhiko Matsuo, Daisuke Nagakubo, Yuhei Komori, Shun Fujisato, Natsumi Takeda, Mizuki Kitamatsu, Keiji Nishiwaki, Ying-Shu Quan, Fumio Kamiyama, Naoki Oiso, Akira Kawada, Osamu Yoshie, Takashi Nakayama
Atopic dermatitis (AD) is a chronic inflammatory skin disease involving Th2 cells, eosinophils, and mast cells. Although CCR4 is a major chemokine receptor expressed on Th2 cells and regarded as a potential therapeutic target for allergic diseases, its role in AD still remains unclear. Here, by using a hydrogel patch as a transcutaneous delivery device for ovalbumin (an antigen) and Staphylococcus aureus δ-toxin (a mast cell activator), we efficiently induced acute AD-like skin lesions in BALB/c mice, a strain prone to Th2 responses, that were characterized by (1) increased numbers of eosinophils, mast cells, and CCR4-expressing Th2 cells in the skin lesions, (2) elevated levels of total and ovalbumin-specific IgE in the sera, and (3) increased expression of IL-4, IL-17A, IL-22, CCL17, CCL22, and CCR4 in the skin lesions...
March 3, 2018: Journal of Investigative Dermatology
Lara A Aqrawi, Janicke Liaaen Jensen, Gunnvor Øijordsbakken, Ann-Kristin Ruus, Ståle Nygård, Marit Holden, Roland Jonsson, Hilde Kanli Galtung, Kathrine Skarstein
A characteristic feature of primary Sjögren's syndrome (pSS) is the destruction of salivary and lacrimal glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG) tissue area, although little is known about their significance in pSS. We have previously investigated adipose tissue infiltration in SG biopsies from pSS patients and non-SS sicca controls. Our findings indicated the distinct incidence of adipose tissue replacement in pSS patients, where adipocytes were detected in interleukin (IL) 6 rich regions...
March 5, 2018: Autoimmunity
Omar M Rahal, Adam R Wolfe, Pijus K Mandal, Richard Larson, Sanda Tin, Cristina Jimenez, Dadong Zhang, Janet Horton, James M Reuben, John S McMurray, Wendy A Woodward
PURPOSE: To determine the role of macrophage polarization on the response of inflammatory breast cancer (IBC) cells to radiation and whether modulation of macrophage plasticity can alter radiation response. METHODS AND MATERIALS: The human THP-1 monocyte cell line and primary human monocytes isolated from peripheral blood mononuclear cells were differentiated into macrophages and polarized to either an "antitumor" (M1) or a "protumor" (M2) phenotype...
March 15, 2018: International Journal of Radiation Oncology, Biology, Physics
Sofia P Rebelo, Catarina Pinto, Tatiana R Martins, Nathalie Harrer, Marta F Estrada, Pablo Loza-Alvarez, José Cabeçadas, Paula M Alves, Emilio J Gualda, Wolfgang Sommergruber, Catarina Brito
The tumour microenvironment (TME) shapes disease progression and influences therapeutic response. Most aggressive solid tumours have high levels of myeloid cell infiltration, namely tumour associated macrophages (TAM). Recapitulation of the interaction between the different cellular players of the TME, along with the extracellular matrix (ECM), is critical for understanding the mechanisms underlying disease progression. This particularly holds true for prediction of therapeutic response(s) to standard therapies and interrogation of efficacy of TME-targeting agents...
May 2018: Biomaterials
Daniela Schwotzer, Monika Niehof, Dirk Schaudien, Heiko Kock, Tanja Hansen, Clemens Dasenbrock, Otto Creutzenberg
BACKGROUND: Understanding the molecular mechanisms of nanomaterial interacting with cellular systems is important for appropriate risk assessment. The identification of early biomarkers for potential (sub-)chronic effects of nanoparticles provides a promising approach towards cost-intensive and animal consuming long-term studies. As part of a 90-day inhalation toxicity study with CeO2 NM-212 and BaSO4 NM-220 the present investigations on gene expression and immunohistochemistry should reveal details on underlying mechanisms of pulmonary effects...
February 20, 2018: Journal of Nanobiotechnology
Gina T Bardi, Mary Ann Smith, Joshua L Hood
Macrophages are key participants in melanoma growth and survival. In general, macrophages can be classified as M1 or M2 activation phenotypes. Increasing evidence demonstrates that melanoma exosomes also facilitate tumor survival and metastasis. However, the role of melanoma exosomes in directly influencing macrophage function is poorly understood. Herein, we investigated the hypothesis that natural melanoma exosomes might directly influence macrophage polarization. To explore this hypothesis, ELISA, RT-qPCR, and macrophage functional studies were performed in vitro using an established source of melanoma exosomes (B16-F10)...
February 16, 2018: Cytokine
Abdollah Jafarzadeh, Sayyed Vahab Azizi, Zahra Arabi, Rayhaneh Ahangar-Parvin, Marziyeh Mohammadi-Kordkhayli, Tiziana Larussa, Fariba Khatami, Maryam Nemati
OBJECTIVES: A spectrum of immunomodulatory properties was attributed to vitamin D (VD). Here, the VD effects on expression of some Th17 cell- related cytokines, chemokines and chemokine receptors were investigated in experimental autoimmune encephalomyelitis (EAE). METHODS: One group of C57BL/6 mice, considered as healthy group, was treated with phosphate buffered saline (PBS). EAE was induced in other three groups and treated from day +3 to +30 with PBS, olive oil (VD vehicle) or 200 ng of VD...
February 15, 2018: Nutritional Neuroscience
Tae-Dong Jung, Sun-Il Choi, Seung-Hyun Choi, Bong-Yeon Cho, Wan-Sup Sim, Sang Jong Lee, Seon Ju Park, Dan-Bi Kim, Young-Cheul Kim, Jin-Ha Lee, Ok-Hwan Lee
Sesame is an important oilseed crop, which has been used as a traditional health food to ameliorate the prevention of various diseases. We evaluated the changes in the anti-allergic activities of sesame by bioconversion. SDS-PAGE of non-fermented sesame proteins showed major allergen bands, while that of fermented sesame showed only a few protein bands. Additionally, we investigated the effectiveness of fermented sesame by bioconversion in tumor necrosis factor-α (TNF-α)- and interferon-γ (IFN-γ)-induced HaCaT cells...
February 14, 2018: Nutrients
Eleonora Cremonesi, Valeria Governa, Jesus Francisco Glaus Garzon, Valentina Mele, Francesca Amicarella, Manuele Giuseppe Muraro, Emanuele Trella, Virginie Galati-Fournier, Daniel Oertli, Silvio Raffael Däster, Raoul A Droeser, Benjamin Weixler, Martin Bolli, Raffaele Rosso, Ulrich Nitsche, Nina Khanna, Adrian Egli, Simone Keck, Julia Slotta-Huspenina, Luigi M Terracciano, Paul Zajac, Giulio Cesare Spagnoli, Serenella Eppenberger-Castori, Klaus-Peter Janssen, Lubor Borsig, Giandomenica Iezzi
OBJECTIVE: Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. DESIGN: Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues...
February 6, 2018: Gut
Zhenyu Zhao, Lvyan Tao, Aihua Liu, Mingbiao Ma, Haiyi Li, Hua Zhao, Jiaru Yang, Shiming Wang, Yirong Jin, Xian Shao, Fukai Bao
Lyme disease, caused by the bacterial spirochete Borrelia burgdorferi, is a tick‑borne zoonosis. Lyme neuroborreliosis is a principal manifestation of Lyme disease and its pathogenesis remains incompletely understood. Recent studies have demonstrated that Borrelia burgdorferi lipoproteins caused similar inflammatory effects as exhibited in Lyme neuroborreliosis. Basic membrane protein A (BmpA) is one of the dominant lipoproteins in the Borrelia burgdorferi membrane. In addition, nuclear factor κ‑B (NF‑κB) modulates the regulation of gene transcription associated with immunity and inflammation; however, in unstimulated cells, NF‑κB is combined with the inhibitor of NF‑κB (IκB‑β)...
January 31, 2018: Molecular Medicine Reports
Colin A Bretz, Vladimir Divoky, Josef Prchal, Eric Kunz, Aaron B Simmons, Haibo Wang, Mary Elizabeth Hartnett
Erythropoietin (EPO) is recognized for neuroprotective and angiogenic effects and has been associated with aging and neovascular age-related macular degeneration (AMD). We hypothesized that systemic EPO facilitates the development of choroidal neovascularization (CNV). Wild type mice expressed murine EPOR (mWtEPOR) in RPE/choroids at baseline and had significantly increased serum EPO after laser treatment. To test the role of EPO signaling, we used human EPOR knock-in mice with the mWtEPOR gene replaced by either the human EPOR gene (hWtEPOR) or a mutated human EPOR gene (hMtEPOR) in a laser-induced choroidal neovascularization (LCNV) model...
February 1, 2018: Scientific Reports
Rui Lin, Yeon Ho Choi, David A Zidar, Julia K L Walker
Allergic asthma is a complex inflammatory disease that leads to significant healthcare costs and reduction in quality of life. Although many cell types are implicated in the pathogenesis of asthma, CD4+ T helper type 2 cells (Th2) are centrally involved. We previously reported that the asthma phenotype is virtually absent in ovalbumin-sensitized and -challenged mice that lack global expression of βarrestin-2 and that CD4+ T cells from these mice displayed significantly reduced C-C motif chemokine 22 (CCL22)-mediated chemotaxis...
January 23, 2018: American Journal of Respiratory Cell and Molecular Biology
Ina Herrmann, Jelena Gotovina, Judit Fazekas-Singer, Michael B Fischer, Karin Hufnagl, Rodolfo Bianchini, Erika Jensen-Jarolim
The M2a subtype of macrophages plays an important role in human immunoglobulin E (IgE-mediated allergies) and other Th2 type immune reactions. In contrast, very little is known about these cells in the dog. Here we describe an in-vitro method to activate canine histiocytic DH82 cells and primary canine monocyte-derived macrophages (MDMs) toward the M2a macrophages using human cytokines. For a side-by-side comparison, we compared the canine cells to human MDMs, and the human monocytic cell line U937 activated towards M1-and M2a cells on the cellular and molecular level...
January 9, 2018: Developmental and Comparative Immunology
Stephanie E Ander, Elizabeth N Rudzki, Nitin Arora, Yoel Sadovsky, Carolyn B Coyne, Jon P Boyle
Toxoplasma gondii is a major source of congenital disease worldwide, but the cellular and molecular factors associated with its vertical transmission are largely unknown. In humans, the placenta forms the key interface between the maternal and fetal compartments and forms the primary barrier that restricts the hematogenous spread of microorganisms. Here, we utilized primary human trophoblast (PHT) cells isolated from full-term placentas and human midgestation chorionic villous explants to determine the mechanisms by which human trophoblasts restrict and respond to T...
January 9, 2018: MBio
Ivana M Lalić, Rudolf Bichele, Anja Repar, Sanja Z Despotović, Saša Petričević, Martti Laan, Pärt Peterson, Jürgen Westermann, Živana Milićević, Ivana Mirkov, Novica M Milićević
It is well known that bacterial lipopolysaccharide (LPS) induces migration of several cellular populations within the spleen. However, there are no data about the impact of LPS on B and T lymphocytes present in the red pulp. Therefore, we used an experimental model in which we tested the effects of intravenously injected LPS on the molecular, cellular and structural changes of the spleen, with special reference to the red pulp lymphocytes. We discovered that LPS induced a massive relocation of B and T lymphocytes from the splenic red pulp, which was independent of the tumor necrosis factor receptor-1 signaling axis...
December 28, 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Xin Zhang, Jing Zheng, Li Zhang, Ying Liu, Gai Ping Chen, Hong Ping Zhang, Lei Wang, De Ying Kang, Lisa G Wood, Gang Wang
BACKGROUND: Obesity negatively impacts asthma control, but the inflammatory mechanisms are poorly understood. OBJECTIVE: To explore which systemic inflammatory mediators mediate the effects of obesity on asthma control. METHODS: The subjects with stable asthma (n = 108) underwent assessment of clinical characteristics, which included using The Asthma Control Questionnaire (ACQ)-6. Obesity was defined as a body mass index (BMI) of ≥30 kg/m2, overweight was defined as BMI between 25 to 29...
January 2, 2018: Allergy and Asthma Proceedings:
Meiyu Peng, Qi Zhang, Yingnan Cheng, Shuyu Fu, Huipeng Yang, Xiangdong Guo, Jieyou Zhang, Lina Wang, Lijuan Zhang, Zhenyi Xue, Yan Li, Yurong Da, Zhi Yao, Liang Qiao, Rongxin Zhang
Pancreatic cancer is an aggressive malignancy that is unresponsive to conventional radiation and chemotherapy. Therefore, development of novel immune therapeutic strategies is urgently needed. L-4F, an Apolipoprotein A-I (ApoA-I) mimetic peptide, is engineered to mimic the anti-inflammatory and anti-oxidative functionalities of ApoA-I. In this work, H7 cells were orthotopically implanted in C57BL/6 mice and treated with L-4F. Then, pancreatic cancer progression and the inflammatory microenvironment were investigated in vivo...
November 21, 2017: Oncotarget
Hye-Sun Lim, Sae-Rom Yo, Mee-Young Lee, Chang-Seob Seo, Hyeun-Kyoo Shin, Soo-Jin Jeong
Inflammatory skin disease are caused by multiple factors, including susceptibility genes, and immunologic and environmental factors, and are characterized by an increase in epidermal thickness and the infiltration of macrophages, keratinocytes, mast cells, eosinophils and other inflammatory cells. Keratinocytes may serve an important role in the pathogenesis of inflammatory skin diseases. The traditional herbal decoction Hyangso‑san (HSS) has been used to treat symptoms of the common cold, including headache, pantalgia, fever and chills...
February 2018: Molecular Medicine Reports
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