IL-37 inhibits osteoporosis via regulating M-CSF and inhibiting IL-6-JAK2/STAT3 signaling pathway / 中国免疫学杂志

Objective:To investigate the mechanism of IL-37 in inhibiting osteoporosis. Methods:Ninety-seven patients with osteoporosis and eighty-one fracture surgery patients without osteoporosis in our hospital from Jan 2013 to Dec 2015 were selected as study subjects. The serum level of IL-37 and IL-6 were detected. Construction of IL-37 transgenic mice, the C57BL/6J mice, IL-37 transgenic mice were set in sham operation group ( Sham ) , operation group ( ovariectomy, OVX ) respectively. The serum level of estrogen,alkaline phosphatase( ALP) ,calcium and phosphorus were detected after 8 weeks. The bilateral femur and spine of mice were collect after sacrifice,the morphology and structure of the femur were analyzed,and the bone density was measured by bone density me-ter. The bone marrow stromal cells( BMSCs) were isolated and cultured in vitro. The proliferation ability of BMSCs,expression of M-CSF and IL-6,and the activation of STAT3 were detected. IL-37 was transfected into mouse osteoblast MC3T3-E1 cell,M-CSF and IL-6 in cultured supernatant were measured by ELISA. Apoptosis of MC3T3-E1 cells were detected by flow cytometry. The activation of STAT3 was detected by Western blot. Results:The serum level of IL-37 in patients with osteoporosis were significantly lower than control group (P<0. 05),while IL-6 was significantly higher than control group(P<0. 05). The serum level of estrogen,calcium and phosphorus in OVX group of C57BL/6J mice and IL-37 transgenic mice were significantly lower than the sham operation group(P<0. 05),while the level of ALP was significantly higher than sham operation group ( P<0. 05 ) , but the serum level of calcium and phosphorus in OVX group of IL-37 transgenic mice were significantly higher than C57BL/6J mice(P<0. 05). The pathological section of femur and spine BMD showed that the bone tissue in C57BL/6J mice and IL-37 transgenic mice in OVX group were damaged and the bone density decreased significantly,but IL-37 transgenic mice was significantly better than C57BL/6J mice(P<0. 05). The proliferation ability BMSCs in OVX group of IL-37 transgenic mice was significantly higher than C57BL/6J,while the activation of STAT3 and expression of M-CSF were significantly lower than C57BL/6J(P<0. 05). The expression of M-CSF and IL-6 were inhibited after MC3T3-E1 cell was transfected with IL-37,and the activation of STAT3 were also inhibited after IL-37 transfection. The results of flow cytometry showed that IL-37 could significantly inhibit the apoptosis of MC3T3-E1 cells. Conclusion:The serum level of IL-37 in patients with osteoporosis decreased significantly. IL-37 may inhibit the proliferation of BMSCs and inhibit the apoptosis of osteoblasts by regulating the expression of M-CSF and the activation of IL-6-JAK2/STAT3 signaling pathway.

IL-37 inhibits osteoporosis via regulating M-CSF and inhibiting IL-6-JAK2/STAT3 signaling pathway / 中国免疫学杂志

Objective:To investigate the mechanism of IL-37 in inhibiting osteoporosis. Methods:Ninety-seven patients with osteoporosis and eighty-one fracture surgery patients without osteoporosis in our hospital from Jan 2013 to Dec 2015 were selected as study subjects. The serum level of IL-37 and IL-6 were detected. Construction of IL-37 transgenic mice, the C57BL/6J mice, IL-37 transgenic mice were set in sham operation group ( Sham ) , operation group ( ovariectomy, OVX ) respectively. The serum level of estrogen,alkaline phosphatase( ALP) ,calcium and phosphorus were detected after 8 weeks. The bilateral femur and spine of mice were collect after sacrifice,the morphology and structure of the femur were analyzed,and the bone density was measured by bone density me-ter. The bone marrow stromal cells( BMSCs) were isolated and cultured in vitro. The proliferation ability of BMSCs,expression of M-CSF and IL-6,and the activation of STAT3 were detected. IL-37 was transfected into mouse osteoblast MC3T3-E1 cell,M-CSF and IL-6 in cultured supernatant were measured by ELISA. Apoptosis of MC3T3-E1 cells were detected by flow cytometry. The activation of STAT3 was detected by Western blot. Results:The serum level of IL-37 in patients with osteoporosis were significantly lower than control group (P<0. 05),while IL-6 was significantly higher than control group(P<0. 05). The serum level of estrogen,calcium and phosphorus in OVX group of C57BL/6J mice and IL-37 transgenic mice were significantly lower than the sham operation group(P<0. 05),while the level of ALP was significantly higher than sham operation group ( P<0. 05 ) , but the serum level of calcium and phosphorus in OVX group of IL-37 transgenic mice were significantly higher than C57BL/6J mice(P<0. 05). The pathological section of femur and spine BMD showed that the bone tissue in C57BL/6J mice and IL-37 transgenic mice in OVX group were damaged and the bone density decreased significantly,but IL-37 transgenic mice was significantly better than C57BL/6J mice(P<0. 05). The proliferation ability BMSCs in OVX group of IL-37 transgenic mice was significantly higher than C57BL/6J,while the activation of STAT3 and expression of M-CSF were significantly lower than C57BL/6J(P<0. 05). The expression of M-CSF and IL-6 were inhibited after MC3T3-E1 cell was transfected with IL-37,and the activation of STAT3 were also inhibited after IL-37 transfection. The results of flow cytometry showed that IL-37 could significantly inhibit the apoptosis of MC3T3-E1 cells. Conclusion:The serum level of IL-37 in patients with osteoporosis decreased significantly. IL-37 may inhibit the proliferation of BMSCs and inhibit the apoptosis of osteoblasts by regulating the expression of M-CSF and the activation of IL-6-JAK2/STAT3 signaling pathway.

The influence of protein malnutrition on the production of GM-CSF and M-CSF by macrophages

ABSTRACT It is well established that protein malnutrition (PM) impairs immune defenses and increases susceptibility to infection. Macrophages are cells that play a central role in innate immunity, constituting one of the first barriers against infections. Macrophages produce several soluble factors, including cytokines and growth factors, important to the immune response. Among those growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). GM-CSF and M-CSF are important to monocyte and macrophage development and stimulation of the immune response process. Knowing the importance of GM-CSF and M-CSF, we sought to investigate the influence of PM on macrophage production of these growth factors. Two-month-old male BALB/c mice were subjected to PM with a low-protein diet (2%) and compared to a control diet (12%) mouse group. Nutritional status, hemogram and the number of peritoneal cells were evaluated. Additionally, peritoneal macrophages were cultured and the production of GM-CSF and M-CSF and mRNA expression were evaluated. To determine if PM altered macrophage production of GM-CSF and M-CSF, they were stimulated with TNF-α. The PM animals had anemia, leukopenia and a reduced number of peritoneal cells. The production of M-CSF was not different between groups; however, cells from PM animals, stimulated with or without TNF-α, presented reduced capability to produce GM-CSF. These data imply that PM interferes with the production of GM-CSF, and consequently would affect the production and maturation of hematopoietic cells and the immune response.

Plasma Levels and Diagnostic Utility of Macrophage Colony-Stimulating Factor, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinases-1 as New Biomarkers of Breast Cancer

BACKGROUND: Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-9 (MMP-9), and its specific tissue inhibitor - tissue inhibitor of metalloproteinases-1 (TIMP-1) may play an important role in the pathogenesis and spread of cancer. We investigated the plasma levels of M-CSF, MMP-9, and TIMP-1 in comparison with a commonly accepted tumor marker CA 15-3 in breast cancer patients and in control groups. METHODS: The cohort included 110 breast cancer patients in groups at stages I-IV. The control group consisted of 50 healthy volunteers and 50 benign tumor patients. Plasma levels of M-CSF, MMP-9, and TIMP-1 were determined by using ELISA, while CA 15-3 concentrations were determined by using chemiluminescent microparticle immunoassay (CMIA). RESULTS: The results showed significant differences in concentrations of the analyzed parameters and in levels of CA 15-3 between the groups of breast cancer patients and the two control groups. Diagnosis using these markers was equal to that using CA 15-3 in terms of sensitivity, predictive values of positive and negativetest results (PPV, NPV) and area under the ROC curve (AUC) in the studied groups. The diagnostic specificities of MMP-9, TIMP-1, M-CSF, and CA 15-3 showed equally high values (95%). The combined use of all tested parameters with CA 15-3 resulted in increased sensitivity, NPV, and AUC, especially in the combination of M-CSF with tumor markers (76%, 64%, and 0.8653). CONCLUSIONS: These findings suggest the tested parameters are useful in the diagnosis of breast cancer patients (except stage I), when combined with CA 15-3.

Análise comparativa da imunoexpressão de GLUT-1, GLUT-3 e M-CSF em lesão periférica e central de células gigantes / Comparative analysis of GLUT-1, GLUT-3 and M-CSF immunoexpression in peripheral and central giant cell lesions

A lesão periférica de células gigantes (LPCG) e a lesão central de células gigantes (LCCG) são patologias histologicamente semelhantes que acometem a região de cabeça e pescoço. O estudo objetivou analisar a expressão imuno-histoquímica dos marcadores GLUT-1, GLUT-3 e M-CSF em uma série de casos de LPCG e LCCG, na tentativa de compreender os diferentes comportamentos biológicos destas entidades patológicas. A amostra foi constituída por 20 espécimes teciduais de LPCG, 20 de lesão central de células gigantes não agressivas (LCCGNA) e 20 de lesão central de células gigantes agressivas (LCCGA), oriundos do Serviço de Anatomia Patológica da Disciplina de Patologia Oral do Departamento de Odontologia da UFRN. Foi realizada a análise semiquantitativa e qualitativa da expressão imuno-histoquímica dos marcadores nas células gigantes e nas células mononucleares. Em relação ao GLUT-1, verificou-se uma diferença estatisticamente significativa na quantidade de células mononucleares imunomarcadas entre a LPCG e a LCCGNA e entre a LPCG e a LCCGA. Em relação à intensidade da marcação também foi verificado uma diferença estatisticamente significativa tanto para as células mononucleares quanto para as células gigantes entre LPCG e LCCGNA e entre LPCG e LCCGA, nas células gigantes também ocorreu uma diferença estatisticamente significativa entre a LCCGNA e a LCCGA. Em relação ao GLUT-3, foi encontrada uma diferença estatisticamente significativa entre LPCG e LCCGA e entre LCCGNA e LCCGA na quantidade de células mononucleares imunomarcadas. No que concerne à intensidade de marcação para a referida proteína foi verificado uma diferença estatisticamente significativa nas células gigantes entre LPCG e LCCGA. Para o M-CSF foi observada apenas uma diferença estatisticamente significativa na intensidade de marcação nas células mononucleares entre LPCG e LCCGNA e entre LPCG e LCCGA. Com base nestes resultados, pode-se concluir a participação do GLUT-1, GLUT-3 e do M-CSF na patogênese das lesões estudadas. A maior imunomarcação destas proteínas nas células mononucleares evidenciam que tais células desempenham uma maior atividade metabólica e osteoclastogênica, principalmente nas LCCGA. Constatou-se que as células mononucleares estavam mais relacionadas à patogênese das lesões estudadas do que propriamente as células gigantes (AU).

The peripheral giant cell lesion (PGCL) and the central giant cell lesion (CGCL) are lesions histologically similar affecting the head and neck region. The study aimed to analyze the immunohistochemical expression of markers GLUT-1, GLUT-3 and MCSF in a series of cases of PGCL and CGCL, in trying to understand the different biological behavior of these pathologies. The sample consisted of 20 tissue specimens of PGCL 20 central lesion of not aggressive giant cell (CLNAGC) and 20 central lesion of aggressive giant cell (CLAGC), coming from the Pathology Unit of Oral Pathology of the Department of Dentistry of UFRN. Was performed the semi-quantitative and qualitative analysis of immunohistochemical expression of the markers in giant cells and mononuclear cells. In relation to the GLUT-1, it was found a statistically significant difference (p <0.05) in the number of mononuclear cells immunomarked between the PGCL and the CLNAGC and between the PGCL and CLAGC. Regarding the intensity of staining was also observed a statistically significant difference both at the mononuclear cells as in giant cells between PL and CLNAGC and between PGCL and CLAGC, at the giant cells there was also a statistically significant difference between the CLNAGC and CLAGC. In relation to GLUT-3, was found a statistically significant difference between PGCL and CLAGC and between CLAGC and CLNAGC in amount of mononuclear cells immunomarked. Regarding the intensity of labeling for such protein was found a statistically significant difference at the giant cells between PL and CLAGC. To the M-CSF was observed only a statistically significant difference in the intensity of labeling at the mononuclear cells between PGCL and CLNAGC and between PGCL and CLAGC. Based on these results, we can conclude the participation of GLUT-1, GLUT-3 and M-CSF in the pathogenesis of the lesions studied. The bigger immunostaining of these proteins in mononuclear cells show that these cells perform a higher metabolic activity and osteoclastogenic, especially in CLAGC. It was found that the mononuclear cells were more related to the pathogenesis of the studied lesions than properly the giants cells (AU).

Effect of M-CSF and GM-CSF on migration and VEGF-A expression of breast cancer cell line 4T1 / 肿瘤研究与临床

Objective To investigate the effect of M-CSF and GM-CSF on migration and expression of VEGF-A in breast cancer cell line 4T1.Methods Real-time PCR was used to detect VEGF-A mRNA expression in 4T1 cells treated by 5 ng/ml or 10 ng/ml M-CSF or GM-CSF.Ability of migration and metastasis of 4T1 cells were analyzed by scratch and Transwell assays.Results The relative expression of VEGF-A mRNA at 12 h and 24 h in 4T1 cells treated by 5 ng/ml or 10 ng/ml M-CSF were 17.81±2.49 and 17.48± 5.43,5.15±2.59 and 5.45±4.28,respectively,while those treated by GM-CSF were 9.77±2.39 and 7.61±2.80,6.53±2.41 and 6.30±2.89,respectively.M-CSF and GM-CSF can promote the expression of VEGF-A in 4T1 cells (P ＜ 0.05).The relative expression of VEGF-A was higher in 4T1 cells treated for 12 h than that for 24 h (P ＜ 0.01).M-CSF,GM-CSF and VEGF-A can promote metastasis of 4T1 cells (all P ＜ 0.05),whereas no gross migration of 4T1 cells was showed by VEGF-A treatment.Conclusion M-CSF and GM-CSF can promote the migration and expression of VEGF-A in breast cancer cell line 4T1.

Establishing a Culture System that Supports in Vitro Expansion of Adult Microglia

Introduction: The vast majority of in vitro research on microglia are based on cells isolated from neonatal animals (3-5 days of age). Studying microglia of adults has been limited by the lack of a suitable culture system that supports their growth. In this study, we describe a protocol for growing microglia of adults based on modifications of the technique for culturing microglia isolated from neonatal rats. Methods: Mixed glia isolated from adult rats (age range of 1 month to 3 years old) were seeded in culture flasks coated with poly-L-lysine. Cells were maintained in DMEM media supplemented with insulin-transferrin-selenium (ITS) and recombinant human macrophage colony-stimulating factor (M-CSF). Mild trypsinisation was carried out to isolate microglia from mixed glia culture. Results: Microglia cells of adult rats were successfully grown in vitro. For the expansion of adult microglia, it was observed that coating the cell culture flasks with poly-L-lysine was crucial to encourage cell adherence. The substitution of insulin in culture media with ITS was found to improve cell yield and reduced the number of days required for culture from 28 days to 14 days. Addition of M-CSF to cell culture medium, along with the improvisations described above provided the best adult microglia cell yield (2.91 ± 0.56 x 10⁶ cells) compared to the technique of replating cells (0.91 ± 0.65 x 10⁶ cells; p<0.05). Conclusion: Optimisation of primary cell culture technique by coating culture flasks with poly-L-lysine,supplementation of culture medium with ITS and M-CSF allowed microglia of adult rats to be successfully cultured in vitro

Effect of Tongmai Liquid on ET,IL-1 8 and M-CSF in patients with coronary heart disease / 中成药

AIM:To observe the effect ofTongmai Liquid on endothelin(ET),interlenkin-18(IL-18),macrophage colony stimulating factor(M-CSF)in patients with coronary heart disease(CHD).METHODS:Eighty patients with coronary heart disease accompanied by heart and spleen qi deficiency and qi stagnanty+phlegm stasis and were randomly assigned into test group and control groups.Forty patients in test group were treated with Tongmai Liquid,30 mL,thrice per day,Forty patients in control group were treated with Shexiang Baoxin Pills,2 pills every time,thrice per day.The therapeutic course for both groups was 30 days.The blood-serum ET,IL-18 and M-CSF had been tested before and after the treatment.RESULTS:The levels of blood-serum ET,IL-18 and MCSF in the two groups decreased significantly after treatment(P＜0.05).There's significant difference in two groups'blood-serum of ET(P＜0.05),There're no significant diffference in two groups'blood-serum level IL-18 and of M-CSF(P＞0.05).CONCLUSION:Tongmai Liquid may decrease blood-serum level of ET,IL-18 and M-CSF in patients with coronary heart disease without side effect.

Production of TGF-beta1 as a Mechanism for Defective Antigen-presenting Cell Function of Macrophages Generated in vitro with M-CSF

BACKGROUND: Macrophages generated in vitro using macrophage-colony stimulating factor (M-CSF) and interleukin (IL)-6 from bone marrow cells (BM-Mp) are defective in antigen presenting cell (APC) function as shown by their ability to induce the proliferation of anti-CD3 mAb-primed syngeneic T cells. However, they do express major histocompatibility (MHC) class I and II molecules, accessory molecules and intracellular adhesion molecules. Here we demonstrate that the defective APC function of macrophages is mainly due to production of TGF-beta1 by BM-Mp. METHODS: Microarray analysis showed that TGF-beta1 was highly expressed in BM-Mp, compared to a macrophage cell line, B6D, which exerted efficient APC function. Production of TGF-beta1 by BM-Mp was confirmed by neutralization experiments of TGF-beta1 as well as by real time-polymerase chain reaction (PCR). RESULTS: Addition of anti-TGF-beta1 monoclonal antibody to cultures of BM-Mp and anti-CD3 mAb-primed syngeneic T cells efficiently induced the proliferation of syngeneic T cells. Conversely, the APC function of B6D cells was almost completely suppressed by addition of TGF-beta1. Quantitative real time-PCR analysis also confirmed the enhanced expression of TGF-beta1 in BM-Mp. CONCLUSION: The defective APC function of macrophages generated in vitro with M-CSF and IL-6 was mainly due to the production of TGF-beta1 by macrophages.

Production of TGF-beta1 as a Mechanism for Defective Antigen-presenting Cell Function of Macrophages Generated in vitro with M-CSF

BACKGROUND: Macrophages generated in vitro using macrophage-colony stimulating factor (M-CSF) and interleukin (IL)-6 from bone marrow cells (BM-Mp) are defective in antigen presenting cell (APC) function as shown by their ability to induce the proliferation of anti-CD3 mAb-primed syngeneic T cells. However, they do express major histocompatibility (MHC) class I and II molecules, accessory molecules and intracellular adhesion molecules. Here we demonstrate that the defective APC function of macrophages is mainly due to production of TGF-beta1 by BM-Mp. METHODS: Microarray analysis showed that TGF-beta1 was highly expressed in BM-Mp, compared to a macrophage cell line, B6D, which exerted efficient APC function. Production of TGF-beta1 by BM-Mp was confirmed by neutralization experiments of TGF-beta1 as well as by real time-polymerase chain reaction (PCR). RESULTS: Addition of anti-TGF-beta1 monoclonal antibody to cultures of BM-Mp and anti-CD3 mAb-primed syngeneic T cells efficiently induced the proliferation of syngeneic T cells. Conversely, the APC function of B6D cells was almost completely suppressed by addition of TGF-beta1. Quantitative real time-PCR analysis also confirmed the enhanced expression of TGF-beta1 in BM-Mp. CONCLUSION: The defective APC function of macrophages generated in vitro with M-CSF and IL-6 was mainly due to the production of TGF-beta1 by macrophages.

Effects of ilexonin A on IL-6 and M-CSF following ballon angioplasty in rabbit common carotid artery / 吉林大学学报(医学版)

Objective To observe the effects of ilexonin A (IA) on IL-6 and M-CSF following ballon angioplasty in rabbit common carotide artery to provide experimental basis for percutaneous coronary interventions. Methods 30 Japanese rabbits were fed with high cholesterol food for 4 weeks. Then they were divided into three groups randomly. Each group had ten rabbits. ①Control group: the incision was sew directly after right carotide artery of the rabbit was seeked. ②Balloon dilation group:the proximal of the carotide artery was cuted,the ballon was delivered and distended,after it was drawn repeatly,the incision was closed. ③IA therapy group: operation was the same to the balloon dilation group,then IA was administered in vein.All of them were fed with high cholesterol diet for 4 weeks and the blood samples were collected 1 d before the operation and 1 d,1,2,4 weeks after the operation. The serum IL-6 and M-CSF levels were determined with radioimmunoassay.The pathological changes of injuried artery were observed. Results ①The IL-6 level in balloon dilation group was higher than that in IA therapy group after the operation (P

CPG OLIGONUCLEOTIDES REGULATE OSTEOCLAST DIFFERENTIATION / 药物分析学报

Objective Bacterial DNA is a pathogen-derived molecule which can regulate the innate immune system by stimulating NF-κB activation. The activity of bacterial DNA relies on its content of unmethylated CpG dinucleotides in particular base contexts("CpG motif"). In light of the pivotal role played by NF-κB in osteoclast differentiation, the ability of CpG oligodeoxynucleotides (CpG ODN) coming from bacterial DNA to modulate osteoclastogenesis was studied. Methods Bone marrow mononuclear cells (BMM) were purified from Balb/c mice, cultured in α-MEM media containing 10% FCS in the presence of mouse M-CSF, with either RANKL or ODNs for 5 days. Osteoclast formation was evaluated on day 5 according to TRAP and May-Grunwald-Giemsa staining. Results CpG ODN alone could induce osteoclast formation in the low degree in BMM culture. The relationship between CpG ODN and RANKL was that CpG ODN could inhibit RANKL-induced osteoclastogenesis when present from the beginning of BMM culture, but strongly increased RANKL-induced osteoclastogenesis in RANKL-pretreated BMMs. Conclusion The mechanism of CpG ODN regulating osteoclast differentiation was bidirectional, which might be a potential therapy for treating metabolic bone disease.

Differentiation of osteoclast-like cells induced from umbilical cord blood cells in vitro / 西安交通大学学报(医学版)

Objective To establish a stable and useful method for culturing human osteoclast-like cells in vitro,and investigate the effect of 1?,25-(OH)2D3,M-CSF and PGE2 on osteoclasts differentiation,proliferation and activation so as to lay the foundation for further study of the biological mechanism for tooth movement.Methods The HCMNC were isolated and cultured in 24-well plate with coverslips and human dentine slices.The experiment group was cultured with 1?,25-(OH)2D3,M-CSF and PGE2,respectively,while the control group was not.The liquid was changed every 3 days and the whole culture process lasted for 7 days.The phase contrast microscopy and TRAP staining were adopted to identify osteoclast-like cells.Results On the 3rd day the monocytes began to fuse and on the 7th day positive multinucleated cells could be seen with TRAP staining,but absorption pit was not formed on the dentin slices.The group with 1?,25-(OH)2D3 had the largest number of osteoclast-like cells.Conclusion After the monocytes in UCB are cultured by 1?,25-(OH)2D3,M-CSF,PGE2 induction,they can turn into TRAP(+) multinucleate osteoclast-like cells,the 1?,25-(OH)2D3 10-8mol/L being the most effective.

Effect of Artorvastatin on Tubulointerstitial Macrophage Proliferation in Unilateral Ureteral Obstructive Nephropathy / 中国医师杂志

Objective To investigate the effect of artorvastatin on macrophage accumulation in tubulointerstitium of unilateral ureteral obstructive (UUO) nephropathy and its possible mechanism.Methods Twenty-one rats were randomly divided into three groups: sham-operatipn, UUO, UUO+ artorvastatin. Immunohistochemistry staining of CD68 and M-CSF was used to define the macrophage accumulation and expression of interstitial M-CSF. Lipid profile in these groups was also determined. Results CD68 + cells and M-CSF expression were significantly increased at day 10 after UUO operation, this kind of CD68 + cell accumulation and M-CSF expression up-regulation were ameliorated by artorvastatin treatment. In UUO and atorvastatin treated groups, the number of macrophage was positively correlated with tubulointerstitial M-CSF expression. There was no significant difference about serum lipid among the three groups. Conclusion Atorvastatin can reduce interstitial macrophage accumulation in UUO nephropathy. This therapeutic effect might relate to down-regulation of tubulointerstitial M-CSF expression.

Effects of Juzen-taiho-to and M-CSF on Thrombocytopenia induced by Anti-cancer Drugs in Gynecologic Malignancies / 日本東洋医学雑誌

We investigated the clinical effect of Juzen-taiho-to and macrophage-colony stimulating factor (M-CSF) on thrombocytopenia induced by anti-cancer chemotherapy in gynecologic malignancies. We discussed 31 courses in 20 patients. Juzen-taiho-to and/or M-CSF were given when indicated from serum platelet level. Twenty-eight courses (90.3%) in 17 patients did not need transfusion of platelet, and 3 courses in 3 patients needed it. It suggested that Juzen-taiho-to and M-CSF might be effective. As platelet-free plasma TGF-β1 level during the treatment of Juzen-taiho-to alone was remarkably increased, it might enhance the antitumoral action. Accordingly, combination treatments of Juzen-taiho-to and M-CSF might be effective for thrombocytopenia induced by anti-cancer chemotherapy.

Analysis of the Effects of Macrophage Colony Stimulating Factor with Image Analysis in Tattoo Removal Using Alexandrite Laser Surgery / 대한피부과학회지

BACKGROUND: Tattoos are acquired pigmented lesions of the skin, and the Q-switched alexandrite laser has been shown to be effective in removing blue-black as well as green, red and mauve colored tattoos. Following the laser therapy, macrophage phagocytes the altered pigment. Macrophage-colony stimulating factor(M-CSF) may influence the macrophage activities. OBJECTIVE: This study was conducted to evaluate the potential adjunctive effect of M-CSF in tattoo removal with laser treatment. METHOD: A prospective study was taken, in 8 guinea pigs and 8 mice, to evaluate the clinical and histopathological clearing of tattoo pigment following the laser treatment of the tattoo at the M-CSF injection site. RESULTS: 1) Clinically, the tattoo resolved more rapidly with Alexandrite laser therapy in the M-CSF treated group. 2) Histopathologically, by using image analysis, there was no significant difference in the relative ratio of dermal tattoo pigment and tattoo containing cells, between laser treated(1.54% in guinea pig, 1.09% in mouse) and laser with M-CSF treated group(1.44% in guinea pig, 0.95% in mouse). CONCLUSION: Our study reveals the role of M-CSF as an adjuvant in tattoo removal using Alexandrite laser surgery. However, further prospective animal studies and human trials, are needed to evaluate the action mechanism of M-CSF at the intradermal injection.

Effect of Granulocyte (-Macrophage) Colony-Stimulating Factor on Oral Mucositis Due to Concomitant Chemoradiotherapy in Locally Advanced Head and Neck Cancer Patients / 中国肿瘤生物治疗杂志

Objective: To evaluate the efficacy of granulocyte(-macrophage) colony stimulating factor[G(M)-CSF] inthe treatment of concomitant chemoradiotherapy-induced oral mucositis in locally advanced head and neck cancer patients.Metheds: Fifteen patients with locally advanced head and neck cancer was received concomitant chemoradiotherapy, whilewhite blood cell count were less than 1. 5?10~9/L with grade Ⅲ/Ⅳ oral mucositis, they were subcutaneously given G(M)-CSF at dose of 100-300?g daily for 3～10 days. Results: After administration of G(M)-CSF, all of the patients had anaugmantation of white blood cell count more than 5. 0?10~9/L. Complete healing of oral mucositis occurred in 1 patient(CR), partial in 8 patients(PR), whereas 6 patients had no change and none was progressive, the objective response rate(CR+PR) was 60%. Condusions: G(M)-CSF is proved effective for oral mucositis caused by concomitant chemoradio-therapy in locally advanced head and neck cancer patients.

Effects of osteoblasts on the formation of osteoclasts in vitro / 西安交通大学学报(医学版)

Objective By culturing the osteoclasts together with the osteoblasts directly to investigate the effect of osteoblasts on the formation of mature osteoclasts.Methods The bone marrow mononuclear cells of rats were treated with 30?g/L M-CSF and 50?g/L RANKL and cultured for 6 days.Subsequently,the primary osteoblasts which were of the same quantity as the osteoclasts were co-cultured directly.In the co-culture system,we added the liquid containing 1,25-(OH)2D3 1?10-8mol/L and PGE2 1?10-6mol/L.The morphological observation,TRAP staining and pit staining were adopted to identify osteoclasts.Results When the osteoclasts were co-cultured with primary osteoblasts,the growth of osteoblasts had more preponderances.After staining,we could see more osteoblasts than osteoclasts.Conclusion The relationship between osteoblasts and osteoclasts is related to the relative quantities of the two cells.When osteoblasts outnumber osteoclasts,osteoblasts would inhibit the formation and differentiation of osteoclasts.

STUDY ON THE PROTECTIVE MECHANISM OF ORGANIC ACIDS IN HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS / 营养学报

Objective: To examine the effects of four organic acids (OA), namely chlorogenic acid (CHA), ascorbic acid (AA), citric acid (CA) and malic acid (MA), on monocyte chemotactic protein-1 (MCP-1) and monocyte colony stimulating factor (M-CSF), as well as on antioxidant function in human vascular endothelial cells (EC). Methods: Original human umbilical vein EC were cultured and incubated for 12 h respectively with ox-LDL, in the presence of CHA, AA, CA and MA at different concentrations(10, 20, 40 mg/L), to study the protective effect on human vascular EC and its mechanism . Results: (1) TBARS value of oxLDL group was 14.85 times higher than that of normal LDL group which was not different with blank group. TBARS values of the OA+oxLDL group were lower at different extents when compared with ox-LDL group, showing dose-effect response. The inhibitory effects of CHA and AA were better than those of CA and MA. (2) MCP-1 and M-CSF of ox-LDL group were higher than those of blank group. Both MCP-1 and M-CSF of OA+ox-LDL groups statistically decreased when compared with ox-LDL group; MCP-1 and M-CSF of single CHA or AA (40 mg/L)group were lower than those of blank group respectively. Conclusion: The protective effects of OA on human vascular EC were contributed to their antioxidant activities, probably through MCP-1 and M-CSF .