Browsing by Subject "macrophage"

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  • Jämsen, Eemeli; Pajarinen, Jukka; Lin, Tzu-hua; Lo, Chi-Wen; Nabeshima, Akira; Lu, Laura; Nathan, Karthik; Eklund, Kari K.; Yao, Zhenyu; Goodman, Stuart B. (2020)
    Macrophage-mediated inflammatory reaction to implant wear particles drives bone loss around total joint replacements (TJR). Although most TJR recipients are elderly, studies linking wear particle-activated macrophages and peri-implant osteolysis have not taken into account the multiple effects that aging has on the innate immune system and, in particular, on macrophages. To address this, we compared the wear particle responses of bone marrow macrophages obtained from young (2-month) and aged (18-month) mice. Macrophages were polarized to M0, M1, or M2 phenotypes in vitro, challenged with titanium particles, and their inflammatory response was characterized at multiple time points by quantitative reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, age-dependent changes in activation of transcription factor nuclear factor-kappa B were analyzed by a lentiviral vector-based luciferase reporter system. The particle stimulation experiment was further repeated using human primary macrophages isolated from blood donors of different ages. We found that the pro-inflammatory responses were generally higher in macrophages obtained from young mice, but differences between the age groups remained small and of uncertain biological significance. Noteworthily, M2 polarization effectively suppressed the particle-induced inflammation in both young and aged macrophages. These results suggest that aging of the innate immune system per se plays no significant role in the response of macrophages to titanium particles, whereas induction of M2 polarization appears a promising strategy to limit macrophage-mediated inflammation regardless of age.
  • Suh, Sang Heon; Choe, Kibaek; Hong, Seon Pyo; Jeong, Seung-hwan; Mäkinen, Taija; Kim, Kwang Soon; Alitalo, Kari; Surh, Charles D.; Koh, Gou Young; Song, Joo-Hye (2019)
    A lacteal is a blunt-ended, long, tube-like lymphatic vessel located in the center of each intestinal villus that provides a unique route for drainage of absorbed lipids from the small intestine. However, key regulators for maintaining lacteal integrity are poorly understood. Here, we explore whether and how the gut microbiota regulates lacteal integrity. Germ depletion by antibiotic treatment triggers lacteal regression during adulthood and delays lacteal maturation during the postnatal period. In accordance with compromised lipid absorption, the button-like junction between lymphatic endothelial cells, which is ultrastructurally open to permit free entry of dietary lipids into lacteals, is significantly reduced in lacteals of germ-depleted mice. Lacteal defects are also found in germ-free mice, but conventionalization of germ-free mice leads to normalization of lacteals. Mechanistically, VEGF-C secreted from villus macrophages upon MyD88-dependent recognition of microbes and their products is a main factor in lacteal integrity. Collectively, we conclude that the gut microbiota is a crucial regulator for lacteal integrity by endowing its unique microenvironment and regulating villus macrophages in small intestine.
  • Taavitsainen, Eveliina (Helsingfors universitet, 2017)
    Chlamydia pneumoniae is an intracellular human pathogen that causes respiratory infections such as pneumonia. Antibodies have been found in serological samples worldwide and most likely every person gets an infection at least once in lifetime. In particular, persistent C.pneumoniae-infection has been associated with multiple chronic diseases such as atherosclerosis, asthma and neurological diseases. C.pneumoniae has a unique two-stage life cycle with two morphological forms; elementary body and reticulate body. In addition, the bacterium has a chronic persistent form. Persistent infection is very typical. Persistent infection can be produced in many ways in vitro, but it has been also found that C.pneumoniae is spontaneously transformed into persistent form in macrophages and monocytes. The aim of this study was to investigate the effect of anti-chlamydial compounds previously identified in the research group on the persistent infektion of C.pneumoniae. For the study, the growth of the bacteria was monitored by qPCR in different cell lines and the compatibility of the compounds with the used persistence model was studied. Four different cell lines were used in the study; HL epithelial cells, Raw264.7 macrophages, THP1 monocytes and macrophages. The effect of compounds on the used cell line was first examined by viability assays. For further studies, C.pneumoniae growth was studied in different cell lines. An qPCR method was set up and used to monitor C.pneumoniae genome copy numbers in infected samples. Based on the growth curves, the measurement points were determined for further studies. Finally, the effect of suitable compounds on C.pneumoniae infection was investigated in epithelial, monocyte and macrophage cell lines. From the investigated compounds, Schisandra chinensis-lingnans were selected for further studies with Raw264.7 cells. The genome number wa not found to decrease compared to the after schisandrin or schisandrin B treatment. In the experiment of the growth of the bacterium, schisandrin-treated samples showed that the genome number of bacterium would be re-grown. This may potentially mean the persistent infection change back to the active form, whereby the bacterium resumed proliferate in the host cell. Based on the results of this study, schisandrin may be considered a potential compound for further studies and a possible model compound for the development of compound against C.pneumoniae infection. However, further studies on the effect of the compounds on persistent infection are needed.
  • Ålgars, Annika; Kemppinen, Lotta; Fair-Mäkelä, Ruth; Mustonen, Harri; Haglund, Caj; Jalkanen, Sirpa (2021)
    Simple Summary Tumor-associated macrophages can either promote or prevent cancer growth depending on factors such as macrophage polarization status, tumor type, and disease stage. Macrophages and vessels interact with each other, and the number of lymphatic vessels also affects cancer survival. CLEVER-1 is a protein expressed both on immunosuppressive M2 macrophages and lymphatic vessels. The aim of this study was to validate our previous results regarding the prognostic role of CLEVER-1(+) macrophages, CD68(+) macrophages, and CLEVER-1(+) lymphatic vessels in stage I-IV colorectal cancer. The results indicate that the prognostic role of tumor-associated macrophages and lymphatic vessels changes during disease progression. The findings resemble our earlier results, but are not completely equal, which may be due to the different types of tumor samples used in the two studies (whole section vs. tissue microarray). Macrophages, which are key players in the tumor microenvironment and affect the prognosis of many cancers, interact with lymphatic vessels in tumor tissue. However, the prognostic role of tumor-associated macrophages (TAM) and lymphatic vessels in human colorectal cancer (CRC) remains controversial. We investigated the prognostic role of CD68(+) and CLEVER-1(+) (common lymphatic endothelial and vascular endothelial receptor 1) TAMs in addition to CLEVER-1(+) lymphatic vessels in 498 stage I-IV CRC patients. The molecular markers were detected by immunohistochemical (IHC) analysis. The results showed that, in early stage I CRC and in young patients (age below median,
  • Al-Rashed, F.; Ahmad, Z.; Iskandar, M.A.; Tuomilehto, J.; Al-Mulla, F.; Ahmad, R. (2019)
    Background/Aims: TNF-α-mediated pro-inflammatory phenotypic change in monocytes is known to be implicated in the pathogenesis of metabolic inflammation and insulin resistance. However, the mechanism by which TNF-α-induces inflammatory phenotypic shift in monocytes is poorly understood. Since long-chain acyl-CoA synthetase 1 (ACSL1) is associated with inflammatory monocytes/macrophages, we investigated the role of ACSL1 in the TNF-α-driven inflammatory phenotypic shift in the monocytes. Methods: Monocytes (Human monocytic THP-1 cells) were stimulated with TNF-α. Inflammatory phenotypic markers (CD16, CD11b, CD11c and HLA-DR) expression was determined with real time RT-PCR and flow cytometry. IL-1β and MCP-1 were determined by ELISA. Signaling pathways were identified by using ACSL1 inhibitor, ACSL1 siRNA and NF-κB reporter monocytic cells. Phosphorylation of NF-κB was analyzed by western blotting and flow cytometry. Results: Our data show that TNF-α induced significant increase in the expression of CD16, CD11b, CD11c and HLA-DR. Inhibition of ACSL1 activity in the cells with triacsin C significantly suppressed the expression of these inflammatory markers. Using ACSL-1 siRNA, we further demonstrate that TNF-α-induced inflammatory markers expression in monocytic cells requires ACSL1. In addition, IL-1b and MCP-1 production by TNF-α activated monocytic cells was significantly blocked by the inhibition of ACSL-1 activity. Interestingly, elevated NF-κB activity resulting from TNF-α stimulation was attenuated in ACSL1 deficient cells. Conclusion: Our findings provide an evidence that TNF-α-associated inflammatory polarization in monocytes is an ACSL1 dependent process, which indicates its central role in TNF-α-driven metabolic inflammation. © 2019 The Author(s).