Dataset Information

Broadleaf Mahonia attenuates granulomatous lobular mastitis?associated inflammation by inhibiting CCL?5 expression in macrophages.

ABSTRACT: Granulomatous lobular mastitis (GLM) is a type of chronic mammary inflammation with unclear etiology. Currently systematic corticosteroids and methitrexate are considered as the main drugs for GLM treatment, but a high toxicity and risk of recurrence greatly limit their application. It is therefore an urgent requirement that safe and efficient natural drugs are found to improve the GLM prognosis. Broadleaf Mahonia (BM) is a traditional Chinese herb that is believed to have anti?inflammatory properties according to ancient records of traditional Chinese medicine. The present study investigated this belief and demonstrated that BM significantly inhibited the expression of interleukin?1? (IL?1?), IL?6, cyclooxygenase?2 and inducible nitric oxide synthase in RAW264.7 cells, but had little influence on the cell viability, cell cycle and apoptosis. Meanwhile, the lipopolysaccharide?induced elevation of reactive oxygen species and nitric oxide was also blocked following BM treatment, accompanied with decreased activity of nuclear factor??B and MAPK signaling. A cytokine array further validated that BM exhibited significant inhibitory effects on several chemoattractants, including chemokine (C?C motif) ligand (CCL)?2, CCL?3, CCL?5 and secreted tumor necrosis factor receptor 1, among which CCL?5 exhibited the highest inhibition ratio in cell and clinical GLM specimens. Collectively, the results show that BM is a novel effective anti?inflammatory herb in vitro and ex vivo, and that CCL?5 may be closely associated with GLM pathogenesis.

SUBMITTER: Wang Z

PROVIDER: S-EPMC5746325 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Broadleaf Mahonia attenuates granulomatous lobular mastitis‑associated inflammation by inhibiting CCL‑5 expression in macrophages.

Wang Zhiyu Z Wang Neng N Liu Xiaoyan X Wang Qi Q Xu Biao B Liu Pengxi P Zhu Huayu H Chen Jianping J Situ Honglin H Lin Yi Y

International journal of molecular medicine 20171109 1

Granulomatous lobular mastitis (GLM) is a type of chronic mammary inflammation with unclear etiology. Currently systematic corticosteroids and methitrexate are considered as the main drugs for GLM treatment, but a high toxicity and risk of recurrence greatly limit their application. It is therefore an urgent requirement that safe and efficient natural drugs are found to improve the GLM prognosis. Broadleaf Mahonia (BM) is a traditional Chinese herb that is believed to have anti‑inflammatory prop ...[more]

PMID: 29138800

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Project description:Background:The exact etiology and pathogenesis of granulomatous lobular mastitis (GLM) are yet to be illuminated. This study aimed to investigate CD68, CD163-positive M2 macrophages, CD57-positive natural killer (NK) cells, and IgG4 in GLM lesion tissue to explore their correlation with the occurrence and clinical features of GLM. Methods:Surgical pathologic specimens of GLM were collected from patients admitted to Hunan Provincial People's Hospital between October, 2014 and October 2015. Based on the postoperative pathological diagnosis, the tissues were divided into 3 groups: the experimental group (GLM, n=36), control group 1 (plasma cell mastitis, PCM, n=17), and control group 2 (breast cystic hyperplasia, n=10). Immunohistochemical staining was carried out using Elivision super testing to detect CD68, CD163, CD57, and IgG4 expression in the pathological tissue samples. The relationship between clinical parameters, including age, reproductive condition, nipple retraction, and tumor size, and the expressions of CD68, CD163, CD57, and IgG4 was analyzed. Results:There was no obvious difference in the levels of CD68, CD163, and CD57 expression between the GLM group and the PCM group, although both groups had higher expression levels of expression than the breast cystic hyperplasia group (P<0.05). In the GLM group, the expression level of CD57 at 2 weeks-3 months was significantly higher than at ?2 weeks (P<0.05). The expression level of CD57 in PCM patients >2 years after lactation was significantly higher than in patients ?2 years after lactation (P<0.05). The level of IgG4 expression in GLM patients with nipple retraction was significantly higher than in those without nipple retraction (P<0.05). Conclusions:Inflammatory cells are closely linked to the occurrence of GLM and PCM. In our study, both the GLM and PCM groups had low expression of IgG4, but the expression level of IgG4 in GLM patients with inverted nipples was significantly higher than that in patients without inverted nipples. This suggests that there may be two different clinical subtypes of GLM. Furthermore, our research also found that NK cells can provide a basis for GLM clinical staging.

Project description:The etiology and pathogenesis of granulomatous lobular mastitis (GLM) remain largely elusive and the expression levels and regulatory roles of microRNAs (miRNAs or miRs) in GLM have remained mostly undetermined. In the present study, the miRNAs that were differentially expressed in breast biopsy samples from patients with GLM and normal tissue adjacent to fibroadenoma were analyzed, a comprehensive differential expression profile of miRNAs was provided and potential biomarkers were screened out. The expression profile of miRNAs was determined by high-throughput sequencing in the tissues of patients with GLM and healthy controls. Significantly differentially expressed miRNAs were screened by threshold setting and cluster analysis and their target genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, circulating differentially expressed miRNAs between the GLM and control groups were further analyzed by reverse transcription-quantitative PCR (RT-qPCR). A total of 31,077 miRNAs were detected by high-throughput sequencing. By using the cutoff criteria of |log2 fold change|>2.5 and q<0.001, 13 miRNAs that were indicated to be GLM biomarkers were screened out. The expression levels of these 13 miRNAs in the GLM group were higher than those in the control group. GO and KEGG enrichment analyses suggested that the occurrence and development of GLM may be associated with autoimmune inflammation, metabolism and pathogenic organisms. miR-451a and miR-5571-3p were confirmed to be significantly increased in the serum of patients with GLM compared with their levels in the serum of healthy volunteers, which suggests that they may be used as biomarkers of GLM. To the best of our knowledge, the present study was the first report detailing genome-wide miRNA profiling of patients with GLM compared with controls. The possible targets and pathways of GLM were evaluated by bioinformatics analysis. The present study identified 13 differentially expressed miRNAs with important theoretical significance and potential application. Furthermore, miR-451a and miR-5571-3p were verified by RT-qPCR as possible biomarkers of GLM.

Project description:BackgroundThe anti-inflammatory properties of the cannabinoid 2 receptor (CB2R) in injury and inflammatory diseases have been widely substantiated. Specifically, the anti-inflammatory effect of CB2R may be achieved by regulating macrophage polarisation. Several research findings suggested that the activation of CB2R could attenuate inflammation by reducing pro-inflammatory M1 macrophage polarisation and promoting anti-inflammatory M2 polarisation. However, considering CB2R inhibits fibrosis and M2 promotes fibrosis, that the activation of CB2R may lead to an increase in M2 macrophages seems contradictory. Therefore, we hypothesised that the activation of CB2R to attenuate inflammation is not achieved by up-regulating M2 macrophages.MethodsWe established an incised wound model using mouse skin and used this to evaluate the effect of CB2R agonists (JWH133 or GP1a) and an antagonist (AM630) on wound healing. At various post-injury intervals, we used western blot analysis, immunofluorescence staining, enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction assays to determine CB2R protein expression, M1/M2 macrophage infiltration, and the protein and gene expression of M1/M2-associated markers and cytokines in skin lesions.ResultsActivation of CB2R significantly reduced M1 macrophage infiltration and slightly increased M2 macrophage infiltration. Similarly, gene expression and protein levels of M1-associated markers and cytokines (interleukin [IL]-6, IL-12, CD86 and inducible nitric oxide synthase) were significantly down-regulated after CB2R agonist administration; in contrast, markers and cytokines were increased in the CB2R antagonist-treated group. Conversely, the administration of agonists slightly increased gene expression and protein levels of M2-associated markers and cytokines (IL-4, IL-10, CD206 and arginase-1 [Arg-1]); however, a statistical significance at most time points post-injury was not noted.ConclusionIn summary, our findings suggested that during incised skin wound healing in mice, increased levels of CB2R may affect inflammation by regulating M1 rather than M2 macrophage subtype polarisation. These results offer a novel understanding of the molecular mechanisms involved in the inhibition of inflammation by CBR2 that may lead to new treatments for cutaneous inflammation.

Dataset Information

Broadleaf Mahonia attenuates granulomatous lobular mastitis?associated inflammation by inhibiting CCL?5 expression in macrophages.

Publications

Broadleaf Mahonia attenuates granulomatous lobular mastitis‑associated inflammation by inhibiting CCL‑5 expression in macrophages.

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