scholarly journals Vitamin D and Macrophage Polarization in Epicardial Adipose Tissue of Atherosclerotic Swine

2018 ◽  
Author(s):  
Palanikumar Gunasekar ◽  
Vicki J. Swier ◽  
Jonathan P. Fleegel ◽  
Chandra S. Boosani ◽  
Mohamed M. Radwan ◽  
...  

AbstractVitamin D functions as a potent immunomodulator by interacting with many immune cells however, its role in regulating inflammation in the epicardial adipose tissue (EAT) is unclear. In the EAT of atherosclerotic microswine that were fed with deficient, sufficient or supplemented levels of vitamin D, we evaluated the phenotype of the macrophages. Vitamin D treatment was continued for 12 months and serum 25(OH)D levels were measured regularly. Infiltration of M1/M2 macrophage was investigated by immunostaining for CCR7 and CD206, respectively in conjunction with a pan macrophage marker CD14. Significant difference in the number of CCR7+ cells was observed in the EAT from vitamin D-deficient swine compared to vitamin D-sufficient or -supplemented swine. Expression of CD206 correlated with high levels of serum 25(OH)D indicating a significant increase in M2 macrophages in the EAT of vitamin D-supplemented compared to -deficient swine. These findings suggest that vitamin D-deficiency exacerbates inflammation by increasing pro-inflammatory M1 macrophages, while vitamin D-supplementation attenuates the inflammatory cytokines and promotes M2 macrophages in EAT. This study demonstrates the significance of vitamin D mediated inhibition of macrophage mediated inflammation in the EAT during coronary intervention in addition to its immunomodulatory role. However, additional studies are required to identify the cellular mechanisms that transduce signals between macrophages and smooth muscle cells during restenosis in the presence and absence of vitamin D.Author Contribution StatementDKA conceived and designed the experiments; PG, JPF, MMR performed the experiments; PG, JPF, VJS analyzed and interpreted the results; PG prepared the figures and wrote the initial draft of the manuscript; CSB, DKA revised and edited the revised manuscript.

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0199411 ◽  
Author(s):  
Palanikumar Gunasekar ◽  
Vicki J. Swier ◽  
Jonathan P. Fleegel ◽  
Chandra S. Boosani ◽  
Mohamed M. Radwan ◽  
...  

2018 ◽  
Vol 8 (2) ◽  
Author(s):  
Achmad Rifa’i ◽  
Handono Kalim ◽  
Kusworini Kusworini ◽  
Cesarius Singgih Wahono

Background : Low level of vitamin D impact the disease activity and the degree of fatigue in SLE patients. This study aims to determine the effect of vitamin D supplementation on disease activity and fatigue condition in Systemic Lupus Erythematosus (SLE) patients with hipovitamin D.Methods: We performed an open clinical trial. Subjects were randomized into two different groups (supplementation or placebo) using simple random sampling. The treatment group got vitamin D3 softgel/ cholecalciferol 1200 IU/day or 30 mg/day, while the control group gotplacebo for 3 months. SLEDAI scores and FSS scores were calculated at pre and posttreatment.Results: There were 20 subjectsfor supplementation group and 19 subjects in the placebo group. From this study, before and after treatment, we found a significant difference of mean level of vitamin D in supplementation group (p=0.000), and no significant difference inpatients with placebo (p=0.427). Moreover, from the SLEDAI score analysis, observed a significant difference bothin the supplemented group (p=0.000) and the placebo group (p=0.006). FSS scores significantly different in the supplemented group (p=0.000). Incorrelation test,there was a negative correlation (r=-0763) between vitamin D level and disease activity (SLEDAI), and both showing stastistical significance between thepre supplementation (p=0.000) and post supplementation (r=-0846; p=0.000). Similarly to theFSS scores, there was a meaningfulnegative correlation (r=-0.931, p=0.000) between the level of vitamin D with FSS scores pre and post supplementation (r=-0.911; p= 0.000). Furthermore, there was a significant correlation between disease activity (SLEDAI) pre supplementation with fatigue condition pre supplementation (r=0.846; p = 0.000) and postsupplementation (r=0.913; p= 0.000).Conclusion: The supplementation of vitamin D 1200 IU per day in patients with SLE improve disease activity and degree of fatigue. Keywords: vitamin D, disease activity, fatigue, SLE


2010 ◽  
Vol 43 (3) ◽  
pp. 141
Author(s):  
Sri Kentjananingsih

Background: Tooth extraction can cause alveolar resorption, and will reduce the denture retention. The process of bone resorption looks like the process of osteoporosis. Calcium and vitamin D supplementation is the rational therapy for minimizing bone loss. Miacalcic is the drug of choice for osteporotic patient. Purpose: This study is aimed to know whether the combination of miacalcic, calcium lactate, and vitamin C are effective in inhibiting post extracted alveolar resorption. Methods: Thirty three healthy postmenopausal women were chosen as samples and they were classified randomly into control group (without treatment), 1st experiment group (treatment was started 3 months post extraction), and 2nd experiment group (treatment was started at the 2nd day post extraction). The treatment was done by giving miacalcic nasal spray, calcium lactate 500 mg and vitamin C 100 mg tablets every morning in 10 days every month for 3 months. X-ray photo of the post extracted area were taken an hour, 3 months, and 6 months post-extraction. Results: After 6 month, there was significant difference in buccolingual thickness decreasing among three groups (p<0.05). The maximum mean difference of buccolingual thickness decreasing was 0.72 mm, between control and 2nd experiment groups. There was no significant difference about decreasing bone density among them (p>0.10). The maximum difference of the mean of density decreasing was 1,906 g/cm2/mm between control and 2nd experiment groups. The increasing density mostly occurred in the 2nd experiment group. Conclusion: The combination of miacalcic, calcium lactate, and vitamin C are effective for inhibiting alveolar resorption, although statistically there was no significant difference about bone density decreasing. The sooner this treatment is given the better result will be achieved.Latar belakang: Pencabutan gigi menyebabkan resorpsi tulang alveolaris, dan akan mengurangi retensi geligi tiruan. Proses resorpsi tulang alveol pada osteoporosis mirip dengan proses resorpsi tulang pada penyembuhan luka bekas pencabutan. Miacalcic adalah obat utama untuk penderita osteoporosis. Kalsium dan vitamin D merupakan terapi yang rasional untuk meminimalkan resorpsi tulang. tujuan: Membuktikan apakah kombinasi miacalcic, kalsium laktat, and vitamin C juga efektif menghambat resorpsi tulang alveol pasca pencabutan. Metode: Sampel 33 wanita postmenopause yang sehat, terbagi secara acak ke dalam kelompok kontrol (tanpa perlakuan), kelompok eksperimen 1 (perlakuan mulai 3 bulan pasca pencabutan) dan kelompok eksperimen 2 (perlakuan mulai hari kedua pasca pencabutan). Perlakuannya yaitu: pemberian miacalcic semprot hidung, tablet kalsium laktat 500 mg dan vitamin C 100 mg setiap pagi, 10 hari dalam sebulan, selama tiga bulan. Foto sinar-X dari regio pasca pencabutan dibuat satu jam, 3 bulan, dan 6 bulan pasca pencabutan. Hasil: 6 bulan pasca-cabut, ada beda bermakna perihal selisih tebal bukolingual tulang alveol antar ketiga kelompok (p<0,05). Rerata penurunan ketebalan ini maksimal sebanyak 0.72 mm, antara kelompok kontrol dan kelompok eksperimen 2. Penurunan kepadatan tulang antar ketiga kelompok tidak bermakna (p>0,10). Beda maksimum rerata kepadatan tulang antara kelompok kontrol dan kelompok eksperimen 2 sebesar 1,906 g/cm2/mm. Peningkatan kepadatan terbanyak dialami anggota kelompok eksperimen 2. Kesimpulan: Kombinasi miacalcic, kalsium laktat, vitamin C efektif menghambat resorpsi tulang alveolaris, walaupun secara statistik beda penurunan kepadatan tidak bermakna. Makin awal pemberian perlakuan, hasilnya akan lebih baik.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Carmen M. Sandoval Pacheco ◽  
Gabriela V. Araujo Flores ◽  
Kadir Gonzalez ◽  
Claudia M. de Castro Gomes ◽  
Luiz F. D. Passero ◽  
...  

Macrophages play important roles in the innate and acquired immune responses against Leishmania parasites. Depending on the subset and activation status, macrophages may eliminate intracellular parasites; however, these host cells also can offer a safe environment for Leishmania replication. In this sense, the fate of the parasite may be influenced by the phenotype of the infected macrophage, linked to the subtype of classically activated (M1) or alternatively activated (M2) macrophages. In the present study, M1 and M2 macrophage subsets were analyzed by double-staining immunohistochemistry in skin biopsies from patients with American cutaneous leishmaniasis (ACL) caused by L. (L.) amazonensis, L. (V.) braziliensis, L. (V.) panamensis ,and L. (L.) infantum chagasi. High number of M1 macrophages was detected in nonulcerated cutaneous leishmaniasis (NUCL) caused by L. (L.) infantum chagasi ( M 1 = 112 ± 12 , M 2 = 43 ± 12 cells/mm2). On the other side, high density of M2 macrophages was observed in the skin lesions of patients with anergic diffuse cutaneous leishmaniasis (ADCL) ( M 1 = 195 ± 25 , M 2 = 616 ± 114 ), followed by cases of localized cutaneous leishmaniasis (LCL) caused by L. (L.) amazonensis ( M 1 = 97 ± 24 , M 2 = 219 ± 29 ), L. (V.) panamensis ( M 1 = 71 ± 14 , M 2 = 164 ± 14 ), and L. (V.) braziliensis ( M 1 = 50 ± 13 , M 2 = 53 ± 10 ); however, low density of M2 macrophages was observed in NUCL. The data presented herein show the polarization of macrophages in skin lesions caused by different Leishmania species that may be related with the outcome of the disease.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wenbo Zhao ◽  
Junxian Hu ◽  
Qingyi He

Abstract Background When multicystic vesicles (precursors of exosomes) are formed in cells, there are two results. One is decomposition by lysosomes, and the other is the generation of exosomes that are transported out through the transmembrane. On the other hand, M2 macrophages promote the formation of local vascularization and provide necessary support for the repair of bone defects. To provide a new idea for the treatment of bone defects, the purpose of our study was to investigate the effect of WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met-NH2) peptide on the secretion of exosomes from murine bone marrow-derived MSCs (mBMSCs) and the effect of exosomes on the polarization of M2 macrophages. Methods The WKYMVm peptide was used to activate the formyl peptide receptor 2 (FPR2) pathway in mBMSCs. First, we used Cell Counting Kit-8 (CCK-8) to detect the cytotoxic effect of WKYMVm peptide on mBMSCs. Second, we used western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) to detect the expression of interferon stimulated gene 15 (ISG15) and transcription factor EB (TFEB) in mBMSCs. Then, we detected lysosomal activity using a lysozyme activity assay kit. Third, we used an exosome extraction kit and western blotting to detect the content of exosomes secreted by mBMSCs. Fourth, we used immunofluorescence and western blotting to count the number of polarized M2 macrophages. Finally, we used an inhibitor to block miRNA-146 in exosomes secreted by mBMSCs and counted the number of polarized M2 macrophages. Results We first found that the WKYMVm peptide had no toxic effect on mBMSCs at a concentration of 1 μmol/L. Second, we found that when the FPR2 pathway was activated by the WKYMVm peptide in mBMSCs, ISG15 and TFEB expression was decreased, leading to increased secretion of exosomes. We also found that lysosomal activity was decreased when the FPR2 pathway was activated by the WKYMVm peptide in mBMSCs. Third, we demonstrated that exosomes secreted by mBMSCs promote the polarization of M2 macrophages. Moreover, all these effects can be blocked by the WRWWWW (WRW4, H-Trp-Arg-Trp-Trp-Trp-Trp-OH) peptide, an inhibitor of the FPR2 pathway. Finally, we confirmed the effect of miRNA-146 in exosomes secreted by mBMSCs on promoting the polarization of M2 macrophages. Conclusion Our findings demonstrated the potential value of the WKYMVm peptide in promoting the secretion of exosomes by mBMSCs and eventually leading to M2 macrophage polarization. We believe that our study could provide a research basis for the clinical treatment of bone defects.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yong You ◽  
Xiaoqing Zhang ◽  
Xiao Wang ◽  
Dan Yue ◽  
Fanxiang Meng ◽  
...  

This study was to identify functions of ILC2, a newly found innate lymphoid cell which mainly locates in mucosa organs like lungs and intestines, in IBD. We injected rIL-33 protein to C57/BL6 mouse to explore how IL-33 induces ILC2 proliferation. The results showed that ILC2 reached a proliferation peak at day 5 and expressed multiple surface markers like CD127, C-kit, CD69, CD44, ST2, CD27, DR3, MHCII, and CD90.2. ILC2 also expressed high quantity of IL-13 and IL-5 and few IL-17A which indicates a potentially immunological function in IBD development. Afterwards, we transferred sort purified ILC2 to Rag1-/- mouse given DSS to induce acute colitis in order to explore the innate function of ILC2. Data showed that ILC2 alleviates DSS-induced acute innate colitis by repairing epithelial barrier and restore body weight. Furthermore, we found that ILC2 can cause macrophages polarizing to M2 macrophages in the gut. Therefore, we concluded that ILC2 played a therapeutic role in mouse acute colitis.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S536-S537
Author(s):  
D Vranesic Bender ◽  
V Domislović ◽  
M Brinar ◽  
D Ljubas Kelečić ◽  
I Karas ◽  
...  

Abstract Background Vitamin D deficiency is frequently present in inflammatory bowel disease (IBD) with a higher incidence in Crohn’s disease (CD) than in ulcerative colitis (UC). Given the involvement of the alimentary tract, many factors can contribute to vitamin D deficiency. The aim of the study was to investigate the association of vitamin D deficiency according to body mass index (BMI) in adult patients with IBD. Methods A cross-sectional study was conducted on a cohort of 152 IBD patients, 68.1% (n = 104) CD and 31.9% (n = 48) UC. The mean age of the total study population was 37.3±11.8 years and 57.3% (n = 87) were male. All patients were adult, Caucasian and without vitamin D supplementation. Patients were recruited during one year period. Results Out of all IBD patients, 60.5% (n = 92) had vitamin D deficiency, 32.2%, (n = 49) insufficiency and 7.2% (n = 11) sufficiency. According to BMI categories there were 12.5% (n = 19) obese patients, 27.6% (n = 42) overweight, 51.3% (n = 78) with normal body weight, and 8.6% (n = 13) underweight. There was a significant difference in vitamin D levels according to different BMI categories in terms of underweight patients having the lowest vitamin D levels; underweight 29.84±11.94 mmol/l, normal 46 ± 20.7 mmol/l, overweight 48±20.1 mmol/l, obese 51±15.3 mmol/l. In addition, there was a significant correlation of vitamin D levels and BMI values (Rho = 0.212, 95% CI 0.069–0.345, p = 0.004), which was more clearly observed in the lower range of BMI values (Figure 1). Male underweight patients had lower levels of vitamin D compared with female patients (26.6 ± 9 vs. 34.7 ± 5.6, p &lt; 0.05). Both patients with CD and UC had significant positive correlation of vitamin D levels and BMI values (UC Rho=0.40, 95% CI 0.16–0.59, p = 0.001, UC Rho = 0.27, 95% CI 0.01–0.05, p = 0.044). However, when comparing vitamin D levels according to phenotype, a significant difference in vitamin D levels was observed in underweight CD (28.4 ± 11.1) comparing to underweight UC patients (40.6 ± 10.6), p &lt; 0.05. In logistic regression analysis, CD phenotype was risk factor for vitamin D deficiency (OR 2.18 95% CI 1.01–4.72, β = 1.22, p = 0.04). Conclusion Our results on untreated IBD patients show a high proportion of vitamin D deficiency both in CD and UC, and significant correlation of vitamin D levels and BMI values, especially in the lower range of BMI values. Moreover, underweight CD patients have lower vitamin D levels comparing to UC. This suggests the need for regular vitamin D monitoring and supplementation especially in IBD patients at risk.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Lucy Pritchard ◽  
Mary Hickson ◽  
Stephen Lewis

AbstractVitamin D (vitD) deficiency is the most common nutritional deficiency worldwide. Most patients are treated with oral vitD capsules (either vitD2 or vitD3). A few studies have reported equal efficacy of buccal spray vitD. This is a new formulation that is absorbed via the oral mucosa into the systemic circulation, bypassing the gastrointestinal route. The main objective of this systematic review was to identify RCT evidence for the comparative effectiveness of buccal spray versus oral vitD on serum 25-hydroxyvitaminD [25-OHD] concentrations and any adverse effects of buccal spray vitD. We have published an a priori protocol using Joanna Briggs Institute (JBI) methodology (PROSPERO CRD42018118580). A three-step search strategy to identify RCTs was conducted, which reported serum 25-OHD concentrations from five databases from 2008–2018. Retrieved abstracts were screened; included papers imported into JBI SUMARI and assessed for study quality (GRADE) by two authors. Meta-analysis was planned. Three RCTs met our inclusion criteria. Due to heterogeneity of studies, meta-analysis was not possible. In a RCT crossover study, mean serum 25-OHD concentrations were significantly higher in patients with malabsorption syndrome (n = 20) on 1000IU buccal spray + 117.8%(10.46, 95%CI6.89,14.03ng/ml) vs.1000IU oral vitD3 + 36.02%(3.96, 95%CI2.37, 5.56ng/ml) at 30days (p < 0.0001). Mean serum 25-OHD were also significantly higher in healthy adults (n = 20) on buccal spray + 42.99%(7.995, 95%CI6.86,9.13ng/ml)vs.oral vitD3 + 21.72%(4.06, 95%CI3.41,4.71ng/ml) at 30days (p < 0.0001). In another RCT crossover study, ANCOVA revealed no significant difference in the mean and SD change from baseline total 25-OHD concentrations in adults (n = 22) on 3000IU buccal spray vs. 3000IU oral vitD3 + 44%,26.15 (SD17.85) vs. + 51%,30.38 (SD17.91)nmol/l, respectively;F = 1.044, adjusted r20.493,p = 0.313 at 4 weeks. In a RCT, 800IU buccal spray was equally effective as 750IU oral vitD3 in children with neurodisabilities(n = 24) at 3 months. Both groups had a significant increase in 25-OHD; 11.5 ng/ml(median8–19) to 26.5(13.6–39)ng/ml and 15.5ng/ml(8–20) to 34.5(22–49)ng/ml, respectively (z = 150;p < 0.0001). The overall certainty of evidence was very low to moderate. No adverse effects were reported. The evidence from these studies suggests that 800IU-3000IU doses of buccal spray vitD3 given daily may be an effective alternative as oral vitD3 in obtaining short-term haematological responses in serum 25-OHD concentrations. Buccal spray vitD3 may be a useful alternative for patients with intestinal malabsorption or dysphagia. Future research should compare buccal spray VD3 to intramuscular injections and confirm these findings in well-designed trials.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi259-vi259
Author(s):  
Lili Chen ◽  
Ming Li

Abstract Guanylate binding protein 1 (GBP1) is an interferon-inducible large GTPase which plays a key role in tumor development, but the molecular mechanism is poorly understood. Here we investigated whether GBP1 could influence the tumor microenvironment in glioblastoma, the most common and malignant brain tumor. We found that forced expression of GBP1 in glioblastoma cells induced macrophage polarization toward an M2 phenotype via upregulating Chemokine (C-C motif) ligand 2 (CCL2). CCL2 acted via its receptor C-C chemokine receptor 2 (CCR2) to enhance macrophage cell migration in vitro. The M2 macrophages in turn promoted glioblastoma cell proliferation and migration. The orthotopic mouse model showed that GBP1 recruited M2 macrophages into tumor to promote glioblastoma progression, and targeting CCL2/CCR2 signaling axis with a small molecule inhibitor RS504393 led to decreased macrophage attraction and M2 polarization and a significant tumor growth retardation and prolonged survival of tumor-bearing mice. Clinically, GBP1 expression positively correlated with M2 macrophage numbers and CCL2 expression in glioblastoma. Taken together, our results reveal that GBP1 modulates the tumor immune microenvironment through CCL2 induction to promote glioblastoma infiltrating growth, and targeting tumor-associated macrophages may represent a new therapeutic strategy against glioblastoma.


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