In Vitro Biocompatibility Evaluation of a New Co-Cr-B Alloy with Potential Biomedical Application

Cobalt–chromium (Co-Cr) alloys have been used in a wide variety of biomedical applications, including dental, cardiovascular, and orthopedic devices. In vitro studies have shown that the mineralization of cells involved in osteogenesis is regulated by boron. The development of a new cobalt-chromium-boron (Co-Cr-B) alloy improves the mechanical properties of the metal, such as wear resistance, and meets biocompatibility requirements. Therefore, the objective of this study was to evaluate the osteogenic differentiation and biocompatibility in in vitro assays. Human dental pulp mesenchymal cells (hDPSCs) were isolated from volunteers and then co-cultured with the Co-Cr plus boron alloy from 0.3% to 1% for 15 days, while the formation of calcium deposits was quantified by Alizarin red staining and the expression of genes was related to osteodifferentiation by RT-qPCR. Simultaneously, the cytotoxicity of our alloy was evaluated by MTT assay and the change in the gene expression of cytokines commonly associated with inflammatory processes. The results showed low cytotoxicity when cells were treated with the Co-Cr-B alloy, and no change in the gene expression of IL-1β, TNF-α, IL-6, and IL-8 was observed compared to the untreated control (p > 0.05). The osteoinduction results shown an increase in mineralization in hDPSCs treated with Co-Cr-B alloy with 1.0% B. In addition, a significant increase in mRNA levels for collagen type 1 in with 0.3% boron and alkaline phosphatase and Runx2 with 0.6% boron were observed. The addition of Boron to the ASTM F75 Co-Cr base alloy improves the biocompatible characteristics. No cytotoxicity and any change of the expression of the pro-inflammatory cytokines IL-1β, TNF-α, IL-6, and IL-8 in human peripheral blood mononuclear cells treated with the cobalt-chromium-boron alloy was observed in vitro assays. Furthermore, our alloy acts as an osteoinductive in osteogenic differentiation in vitro. Therefore, our results could set the standard for the development of in vivo trials and in the future, it could be considered as an alternative for regenerative therapy.

Download Full-text

Determinants of leptin gene expression in fat depots of lean mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00392.2001 ◽

2002 ◽

Vol 282 (1) ◽

pp. R226-R234 ◽

Cited By ~ 75

Author(s):

Yiying Zhang ◽

Kai-Ying Guo ◽

Patricia A. Diaz ◽

Moonseong Heo ◽

Rudolph L. Leibel

Keyword(s):

Gene Expression ◽

Glucocorticoid Receptor ◽

Insulin Receptor ◽

Physiological Role ◽

Mrna Levels ◽

Strongly Correlated ◽

Fat Depots ◽

Tnf Α ◽

Adipocyte Volume

The relationship of leptin gene expression to adipocyte volume was investigated in lean 10-wk-old male C57BL/6J mice. mRNA levels for leptin, insulin receptor, glucocorticoid receptor, and tumor necrosis factor (TNF)-α in inguinal, epididymal, and retroperitoneal adipose tissues were quantified and related to adipocyte volume. Leptin mRNA levels were highly correlated with adipocyte volume within each fat depot. Multiple regression analysis of pooled data from the three depots showed that leptin mRNA levels were strongly correlated with adipocyte volumes (β = 0.84, P < 0.001) and, to a smaller degree, with glucocorticoid receptor mRNA levels (β = 0.36, P < 0.001). Depot of origin had no effect ( P > 0.9). Rates of leptin secretion in vitro were strongly correlated with leptin mRNA levels ( r = 0.89, P < 0.001). mRNA levels for TNF-α, insulin receptor, and glucocorticoid receptor showed no significant correlation with adipocyte volume. These results demonstrate that depot-specific differences in leptin gene expression are mainly related to the volumes of the constituent adipocytes. The strong correlation between leptin gene expression and adipocyte volume supports leptin's physiological role as a humoral signal of fat mass.

Download Full-text

Association of changes in T regulatory cells (Treg) during nivolumab treatment with melanoma outcome.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.3031 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 3031-3031 ◽

Cited By ~ 2

Author(s):

Jeffrey S. Weber ◽

Rupal Ramakrishnan ◽

Andressa Laino ◽

Anders E. Berglund ◽

David Woods

Keyword(s):

Gene Expression ◽

T Cells ◽

Cd4 T Cells ◽

T Regulatory Cells ◽

Mononuclear Cells ◽

In Vitro Assays ◽

Peripheral Blood Mononuclear ◽

Suppressive Function ◽

Blocking Antibodies

3031 Background: PD-1 blocking antibodies have significant efficacy in the treatment of melanoma; however, many patients fail to respond and resistance mechanisms remain unknown. We addressed the role of Tregs, an immunosuppressive T-cell population, in patient outcome after treatment with nivolumab. Methods: Peripheral blood mononuclear cells (PBMC) were obtained from patients on trials with nivolumab as adjuvant therapy for resected disease or as treatment for metastatic melanoma. To measure suppression, Tregs were flow-sorted from PBMC and evaluated in allogeneic mixed lymphocyte reactions. Tregs and conventional CD4 T-cells were evaluated for gene expression changes by RNA-sequencing. Treg percentages and phosphorylated STAT3 (pSTAT3) expression were evaluated by flow cytometry. The effects of PD-1 blockade with nivolumab were evaluated in vitro using T-cells from baseline patient PBMC samples. Results: Tregs from responding patients or adjuvant patients without evidence of disease (NED) had reduced suppressive function post-nivolumab (p < 0.05), but no changes were observed in relapsing/non-responding patients; their Tregs were more suppressive than NED/responding Tregs (p < 0.001). NED Tregs had unique gene expression changes and associated pathways post-nivolumab compared to relapsing patient Tregs and conventional CD4 T-cells, including up-regulation of proliferation pathways (q < 8e-19) and downregulation of oxidative phosphorylation (q < 7e-5). NED Tregs had upregulation of pSTAT3 expression post-nivolumab (p < 0.05), which was not observed in relapsing patients. Evaluation of Tregs from patients with active disease also showed upregulation of pSTAT3 in responders (p < 0.05) but not non-responders. The relative increase in Treg pSTAT3 was associated with increased overall survival (R2= 0.49, p < 0.05). In vitro assays using PD-1 blocking antibodies recapitulated the increase in pSTAT3 (p < 0.05) and Treg percentages (p < 0.001), which were diminished with the addition of a STAT3 inhibitor (p < 0.01). Conclusions: These results demonstrate previously unknown roles of decreased Treg suppressive function and induction of STAT3 as biomarkers of patient’s outcome to nivolumab therapy.

Download Full-text

Effect of a Histone Deacetylases Inhibitor of IL-18 and TNF-Alpha Secretion in Vitro

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2018.075 ◽

2018 ◽

Vol 6 (2) ◽

pp. 269-273

Author(s):

Zlatka Georgieva Dobreva ◽

Boncho Grigorov Grigorov ◽

Spaska Angelova Stanilova

Keyword(s):

Gene Expression ◽

Histone Deacetylases ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor ◽

Inactive Protein

BACKGROUND: Interleukin-18 (IL-18) and Tumor Necrosis Factor-alpha (TNF-α) are proinflammatory cytokines that increased the development of Th1 immune response, but have a different type of regulation of the gene expression. Whereas TNF-α has an inducible expression, IL-18 is translated as an inactive protein and required proteolytic cleavage by Casp-1 in inflammasome complexes.AIM: To investigate the effect of the histone deacetylases inhibitor Suberoylanilide Hydroxamic Acid (SAHA) on the gene expression and secretion of both cytokines, IL-18 and TNF-α, according to their contribution to the cancer development and anticancer immunity.METHODS: Isolated peripheral blood mononuclear cells (PBMC) were stimulated with LPS and C3bgp with or without SAHA. Cytokine production was assessed by ELISA at 6 and 24h.RESULTS: IL-18 and TNF-α secretion was significantly increased at 6h and 24h in response to stimulation. TNF-α production from stimulated PBMC was downregulated by SAHA at 6 and 24h. Treatment with SAHA does not inhibit the secretion of IL-18 significantly either at 6 or 24h of stimulation.CONCLUSION: The inhibition of histone deacetylases by SAHA does not influence the inflammasome-dependent production of immunologically active IL-18. In contrast, the production of proinflammatory TNF-α in cultures was mediated by the activity of HDAC class I and class II enzymes.

Download Full-text

Increased expression of TNF-α, IL-6, and IL-8 in HALS: implications for reduced adiponectin expression and plasma levels

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00206.2003 ◽

2003 ◽

Vol 285 (5) ◽

pp. E1072-E1080 ◽

Cited By ~ 116

Author(s):

Aina S. Lihn ◽

Bjørn Richelsen ◽

Steen B. Pedersen ◽

Steen B. Haugaard ◽

Gulla Søby Rathje ◽

...

Keyword(s):

Gene Expression ◽

Insulin Sensitivity ◽

Highly Active Antiretroviral Therapy ◽

Inhibitory Effect ◽

Mrna Levels ◽

Plasma Adiponectin ◽

Tnf Α ◽

Adiponectin Mrna ◽

Circulating Levels

Human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) is a side effect of highly active antiretroviral therapy of HIV-infected patients; however, the mechanism of the lipodystrophy and insulin resistance seen in this syndrome remains elusive. Adiponectin, an adipocyte-specific protein, is thought to play an important role in regulating insulin sensitivity. We investigated circulating levels and gene expression of adiponectin in subcutaneous abdominal adipose tissue (AT) from 18 HIV-infected patients with HALS compared with 18 HIV-infected patients without HALS. Implications of cytokines for adiponectin levels were investigated by determining circulating levels of TNF-α, IL-6, and IL-8 as well as gene expression of these cytokines in AT. HALS patients exhibited 40% reduced plasma adiponectin levels ( P < 0.05) compared with non-HALS subjects. Correspondingly, adiponectin mRNA levels in AT were reduced by >50% ( P = 0.06). HALS patients were insulin resistant, and a positive correlation was found between plasma adiponectin and insulin sensitivity ( r = 0.55, P < 0.01) and percent limb fat ( r = 0.61, P < 0.01). AT mRNA of TNF-α, IL-6, and IL-8 was increased in AT of HALS subjects ( P < 0.05), and both AT TNF-α mRNA and plasma TNF-α were negatively correlated to plasma adiponectin ( P < 0.05). Finally, TNF-α was found in vitro to inhibit human AT adiponectin mRNA by 80% ( P < 0.05). In conclusion, HALS patients have reduced levels of plasma adiponectin and adiponectin mRNA in AT. Increased cytokine mRNA in AT is hypothesized to exert an inhibitory effect on adiponectin gene expression and, consequently, to play a role in the reduced plasma adiponectin levels found in HALS patients.

Download Full-text

Epigenetic Mechanism of TGF-β1 Promoting Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells in Osteoarthritis

10.21203/rs.3.rs-732375/v1 ◽

2021 ◽

Author(s):

Jianwei He ◽

Weiwei Cao ◽

Qinzheng Fang ◽

Inayat Azeem ◽

Wei Liu

Keyword(s):

Osteogenic Differentiation ◽

Bone Alkaline Phosphatase ◽

Epigenetic Mechanism ◽

Mrna Levels ◽

Osteogenic Medium ◽

Alizarin Red ◽

Expression Levels ◽

Qrt Pcr ◽

Tgf Β1

Abstract Objectives: It had been proved that TGF-β1 was correlated with onset of osteoarthritis in vitro and vivo. Here, This study was to elucidate the epigenetic mechanism of TGF-β1 promoting osteogenic differentiation in osteoarthritis. Methods: hBMSCs surface antigens were assayed by flow cytometry tests. qRT-PCR was performed to detect hBMSCs mRNA levels of RUNX2, PPARγ and SOX9. hBMSCs were stained by osteoalkaline phosphatase and alizarin red. The qRT-PCR and Western blot were both used to detect the expression levels of methylases, demethylases and osteogenic transcription factor RUNX2 after hBMSCs were cultrued in osteogenic medium coincubated with TGF-β1 solution. Results: hBMSCs were identified by over expressions of CD90, CD105 and CD44, as well as the positive multi-diffenentiation potential tests. hBMSCs bone alkaline phosphatase and alizarin red staining were observed to deepen in TGF-β1 group compared with the osteogenic culture group. The mRNA expression levels of EZH1, KDM2B, KDM4A/4B/4C/4D, and KDM6A /6B were increased in hBMSCs cultured in osteogenic medium. The expression levels of KDM6A/6B were shown increasement when TGF-β1 was co-incubated with osteogenic medium. Furthermore, the mRNA and protein levels of KDM6A/6B were significantly decreased after SB431542 was added in the medium. RUNX2 was significantly inhibited by the addition of GSK-J4 solution, while KDM6A/6B expression level did not change significantly. Conclusion: The osteogenic differentiation of hBMSCs was related to the enhanced expressions of EZH1, KDM2B, KDM4A-4D, KDM6A/6B. The expression levels of demethylase KDM6A/6B were positively regulated by the TGF-β/Smad signaling pathway, which promoted the osteogenic differentiation of hBMSCs.

Download Full-text

Establishing a deeper understanding of the osteogenic differentiation of monolayer cultured human pluripotent stem cells using novel and detailed analyses

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02085-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ping Zhou ◽

Jia-Min Shi ◽

Jing-E Song ◽

Yu Han ◽

Hong-Jiao Li ◽

...

Keyword(s):

Stem Cells ◽

Osteogenic Differentiation ◽

Pluripotent Stem Cells ◽

Embryonic Stem ◽

Telomerase Activity ◽

Human Pluripotent Stem Cells ◽

Cell Counting ◽

Cell Type ◽

Alizarin Red

Abstract Background Derivation of osteoblast-like cells from human pluripotent stem cells (hPSCs) is a popular topic in bone tissue engineering. Although many improvements have been achieved, the low induction efficiency because of spontaneous differentiation hampers their applications. To solve this problem, a detailed understanding of the osteogenic differentiation process of hPSCs is urgently needed. Methods Monolayer cultured human embryonic stem cells and human-induced pluripotent stem cells were differentiated in commonly applied serum-containing osteogenic medium for 35 days. In addition to traditional assays such as cell viability detection, reverse transcription-polymerase chain reaction, immunofluorescence, and alizarin red staining, we also applied studies of cell counting, cell telomerase activity, and flow cytometry as essential indicators to analyse the cell type changes in each week. Results The population of differentiated cells was quite heterogeneous throughout the 35 days of induction. Then, cell telomerase activity and cell cycle analyses have value in evaluating the cell type and tumourigenicity of the obtained cells. Finally, a dynamic map was made to integrate the analysis of these results during osteogenic differentiation of hPSCs, and the cell types at defined stages were concluded. Conclusions Our results lay the foundation to improve the in vitro osteogenic differentiation efficiency of hPSCs by supplementing with functional compounds at the desired stage, and then establishing a stepwise induction system in the future.

Download Full-text

Modulatory Effects of Osthole on Lipopolysaccharides-Induced Inflammation in Caco-2 Cell Monolayer and Co-Cultures with THP-1 and THP-1-Derived Macrophages

Nutrients ◽

10.3390/nu13010123 ◽

2020 ◽

Vol 13 (1) ◽

pp. 123

Author(s):

Natalia K. Kordulewska ◽

Justyna Topa ◽

Małgorzata Tańska ◽

Anna Cieślińska ◽

Ewa Fiedorowicz ◽

...

Keyword(s):

Gene Expression ◽

Inflammatory Reaction ◽

Wide Spectrum ◽

Cell Monolayer ◽

In Vivo Studies ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Tnf Α

Lipopolysaccharydes (LPS) are responsible for the intestinal inflammatory reaction, as they may disrupt tight junctions and induce cytokines (CKs) secretion. Osthole has a wide spectrum of pharmacological effects, thus its anti-inflammatory potential in the LPS-treated Caco-2 cell line as well as in Caco-2/THP-1 and Caco-2/macrophages co-cultures was investigated. In brief, Caco-2 cells and co-cultures were incubated with LPS to induce an inflammatory reaction, after which osthole (150–450 ng/mL) was applied to reduce this effect. After 24 h, the level of secreted CKs and changes in gene expression were examined. LPS significantly increased the levels of IL-1β, -6, -8, and TNF-α, while osthole reduced this effect in a concentration-dependent manner, with the most significant decrease when a 450 ng/mL dose was applied (p < 0.0001). A similar trend was observed in changes in gene expression, with the significant osthole efficiency at a concentration of 450 ng/μL for IL1R1 and COX-2 (p < 0.01) and 300 ng/μL for NF-κB (p < 0.001). Osthole increased Caco-2 monolayer permeability, thus if it would ever be considered as a potential drug for minimizing intestinal inflammatory symptoms, its safety should be confirmed in extended in vitro and in vivo studies.

Download Full-text

LPS-induced expression of CD14 in the TRIF pathway is epigenetically regulated by sulforaphane in porcine pulmonary alveolar macrophages

Innate Immunity ◽

10.1177/1753425916669418 ◽

2016 ◽

Vol 22 (8) ◽

pp. 682-695 ◽

Cited By ~ 12

Author(s):

Qin Yang ◽

Maren J Pröll ◽

Dessie Salilew-Wondim ◽

Rui Zhang ◽

Dawit Tesfaye ◽

...

Keyword(s):

Gene Expression ◽

Alveolar Macrophages ◽

Methylation Status ◽

Gene Body ◽

Gene Body Methylation ◽

Tnf Α ◽

Pulmonary Alveolar Macrophages ◽

Cluster Of Differentiation ◽

Cd14 Gene

Pulmonary alveolar macrophages (AMs) are important in defense against bacterial lung inflammation. Cluster of differentiation 14 (CD14) is involved in recognizing bacterial lipopolysaccharide (LPS) through MyD88-dependent and TRIF pathways of innate immunity. Sulforaphane (SFN) shows anti-inflammatory activity and suppresses DNA methylation. To identify CD14 epigenetic changes by SFN in the LPS-induced TRIF pathway, an AMs model was investigated in vitro. CD14 gene expression was induced by 5 µg/ml LPS at the time point of 12 h and suppressed by 5 µM SFN. After 12 h of LPS stimulation, gene expression was significantly up-regulated, including TRIF, TRAF6, NF-κB, TRAF3, IRF7, TNF-α, IL-1β, IL-6, and IFN-β. LPS-induced TRAM, TRIF, RIPK1, TRAF3, TNF-α, IL-1β and IFN-β were suppressed by 5 µM SFN. Similarly, DNMT3a expression was increased by LPS but significantly down-regulated by 5 µM SFN. It showed positive correlation of CD14 gene body methylation with in LPS-stimulated AMs, and this methylation status was inhibited by SFN. This study suggests that SFN suppresses CD14 activation in bacterial inflammation through epigenetic regulation of CD14 gene body methylation associated with DNMT3a. The results provide insights into SFN-mediated epigenetic down-regulation of CD14 in LPS-induced TRIF pathway inflammation and may lead to new methods for controlling LPS-induced inflammation in pigs.

Download Full-text

Differential Effects of Gonadotropin-Releasing Hormone (GnRH) Pulse Frequency on Gonadotropin Subunit and GnRH Receptor Messenger Ribonucleic Acid Levels in Vitro*

Endocrinology ◽

10.1210/endo.138.3.4968 ◽

1997 ◽

Vol 138 (3) ◽

pp. 1224-1231 ◽

Cited By ~ 112

Author(s):

Ursula B. Kaiser ◽

Andrzej Jakubowiak ◽

Anna Steinberger ◽

William W. Chin

Keyword(s):

Gene Expression ◽

Messenger Rna ◽

Pulse Frequency ◽

Gnrh Receptor ◽

Pituitary Cells ◽

Mrna Levels ◽

Subunit Gene ◽

Differential Effects ◽

Messenger Ribonucleic Acid

Abstract The hypothalamic hormone, GnRH, is released and transported to the anterior pituitary in a pulsatile manner, where it binds to specific high-affinity receptors and regulates gonadotropin biosynthesis and secretion. The frequency of GnRH pulses changes under various physiological conditions, and varying GnRH pulse frequencies have been shown to regulate differentially the secretion of LH and FSH and the expression of the gonadotropin α, LHβ, and FSHβ subunit genes in vivo. We demonstrate differential effects of varying GnRH pulse frequency in vitro in superfused primary monolayer cultures of rat pituitary cells. Cells were treated with 10 nm GnRH pulses for 24 h at a frequency of every 0.5, 1, 2, or 4 h. α, LHβ, and FSHβ messenger RNA (mRNA) levels were increased by GnRH at all pulse frequencies. α and LHβ mRNA levels and LH secretion were stimulated to the greatest extent at a GnRH pulse frequency of every 30 min, whereas FSHβ mRNA levels and FSH secretion were stimulated maximally at a lower GnRH pulse frequency, every 2 h. GnRH receptor (GnRHR) mRNA levels also were increased by GnRH at all pulse frequencies and were stimulated maximally at a GnRH pulse frequency of every 30 min. Similar results were obtained when the dose of each pulse of GnRH was adjusted to maintain a constant total cumulative dose of GnRH over 24 h. These data show that gonadotropin subunit gene expression is regulated differentially by varying GnRH pulse frequencies in vitro, suggesting that the differential effects of varying GnRH pulse frequencies on gonadotropin subunit gene expression occur directly at the level of the pituitary. The pattern of regulation of GnRHR mRNA levels correlated with that of α and LHβ but was different from that of FSHβ. This suggests that α and LHβ mRNA levels are maximally stimulated when GnRHR levels are relatively high, whereas FSHβ mRNA levels are maximally stimulated at lower levels of GnRHR expression, and that the mechanism for differential regulation of the gonadotropins by varying pulse frequencies of GnRH may involve levels of GnRHR. Furthermore, these data suggest that the mechanisms whereby varying GnRH pulse frequencies stimulate α, LHβ, and GnRHR gene expression are similar, whereas the stimulation of FSHβ mRNA levels may be different.

Download Full-text

High Matrix Metalloproteinase Production Correlates with Immune Activation and Leukocyte Migration in Leprosy Reactional Lesions

Infection and Immunity ◽

10.1128/iai.00896-09 ◽

2009 ◽

Vol 78 (3) ◽

pp. 1012-1021 ◽

Cited By ~ 17

Author(s):

Rosane M. B. Teles ◽

Rose B. Teles ◽

Thais P. Amadeu ◽

Danielle F. Moura ◽

Leila Mendonça-Lima ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Cultured Cells ◽

Leukocyte Migration ◽

Therapeutic Interventions ◽

Matrix Metalloproteinase 2 ◽

Mrna Levels ◽

Membrane Breakdown ◽

Tnf Α ◽

Ifn Γ

ABSTRACT Gelatinases A and B (matrix metalloproteinase 2 [MMP-2] and MMP-9, respectively) can induce basal membrane breakdown and leukocyte migration, but their role in leprosy skin inflammation remains unclear. In this study, we analyzed clinical specimens from leprosy patients taken from stable, untreated skin lesions and during reactional episodes (reversal reaction [RR] and erythema nodosum leprosum [ENL]). The participation of MMPs in disease was suggested by (i) increased MMP mRNA expression levels in skin biopsy specimens correlating with the expression of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), (ii) the detection of the MMP protein and enzymatic activity within the inflammatory infiltrate, (iii) increased MMP levels in patient sera, and (iv) the in vitro induction of MMP-9 by Mycobacterium leprae and/or TNF-α. It was observed that IFN-γ, TNF-α, MMP-2, and MMP-9 mRNA levels were higher in tuberculoid than lepromatous lesions. In contrast, interleukin-10 and tissue inhibitor of MMP (TIMP-1) message were not differentially modulated. These data correlated with the detection of the MMP protein evidenced by immunohistochemistry and confocal microscopy. When RR and ENL lesions were analyzed, an increase in TNF-α, MMP-2, and MMP-9, but not TIMP-1, mRNA levels was observed together with stronger MMP activity (zymography/in situ zymography). Moreover, following in vitro stimulation of peripheral blood cells, M. leprae induced the expression of MMP-9 (mRNA and protein) in cultured cells. Overall, the present data demonstrate an enhanced MMP/TIMP-1 ratio in the inflammatory states of leprosy and point to potential mechanisms for tissue damage. These results pave the way toward the application of new therapeutic interventions for leprosy reactions.

Download Full-text