Effect of bisphosphonates on production of interleukin 1-like activity by macrophages and its effect on rabbit chondrocytes

Bisphosphonates are potent inhibitors of bone resorption, but their mode of action is still unknown. Since interleukin 1 (IL-1)-like activity has been shown to stimulate bone resorption in vitro, we have studied whether bisphosphonates inhibit either the production of IL-1-like activity or its effect on one type of connective tissue cell, Chondrocytes. The production of IL-1-like activity was examined using rabbit peritoneal macrophages and the murine macrophage cell ine P388D₁, and the effect of IL-1-like activity was assessed by measuring the secretion of collagenase and prostaglandin E₂ (PGE₂) by rabbit Chondrocytes. Production of IL-1-like activity was unaffected by bisphosphonates, whereas the effect of IL-1-like activity on collagenase and prostaglandin E₂ secretion by rabbit Chondrocytes was increased rather than inhibited by bisphosphonates. Finally, bisphosphonates increased DNA and cell number in chondrocyte cultures, but this effect was blocked when IL-1-like activity was added to the cultures. Thus, our results provide no evidence for a direct inhibitory effect of bisphosphonates on either the production of IL-1-like activity or the action of IL-1-like activity on Chondrocytes     

转化生长因子β对白介素-1β诱导人骨关节炎软骨细胞表达NO的影响

目的 探讨转化生长因子β(TGF-β)对白介素-1β(IL-1β)诱导人骨关节炎(osteoarthritis,OA)软骨细胞表达一氧化氮(mitrlc oxide,NO)的影响.方法 体外培养OA患者软骨细胞,施以不同浓度的IL-1β,收集细胞培养液,检测其上清液表达NO的情况;选取某一合适浓度的IL-1β,然后施以不同浓度的TGF-β,检测其上清液表达N0的情况.结果 IL-1β诱导下,软骨细胞增加NO的表达,并呈剂量依赖关系;而TGF-β可抑制IL-1β诱导软骨细胞表达NO的作用,随着TGF-β剂量的加大,抑制N0的作用愈明显.结论 TGF-β具有抑制IL-1β诱导人骨关节炎OA软骨细胞表达NO的作用.TGF-β可能是OA的一种保护因子.     

Effect of phorbol esters on the susceptibility of a glioma cell line to lymphokine-activated killer cell activity

The mechanisms by which lymphokine-activated killer (LAK) cells exert their cytotoxic effects are not well understood. This study demonstrates that phorbol ester pretreatment of a LAK cell-sensitive glioma cell line (SNB-19) induced a significant decrease in the susceptibility of cells to LAK cell-mediated lysis. This effect was produced by low concentrations of the tumor-promoting phorbol ester, phorbol-12,13-myristate acetate (PMA), and was reversible. Protein kinase C (PKC) inhibitors failed to block this phenomenon. No apparent alteration in the ability of LAK cells to bind to their targets was observed. Thus, PMA may have exerted its effects by a mechanism that does not require PKC, or these glioma cells may possess an isozyme of PKC which is insensitive to the inhibitors used in these studies.     

白细胞介素-1受体拮抗蛋白和白细胞介素-10联合基因转染人骨关节炎软骨细胞的研究

目的探讨逆转录病毒载体PLXRN介导的人白细胞介素-1受体拮抗蛋白（hIL-1Ra）和白细胞介素-10（hlL-10）联合基因转染在人骨关节炎（OA）关节软骨细胞中稳定表达的可行性。方法构建含目的基因的表达载体PLXRN-IL-1Ra和PLXRN—IL-10，经酶切及测序鉴定正确后单个或联合转染人OA软骨细胞，逆转录-聚合酶链反应（RT—PCR）检测细胞内目的基因的表达；酶联免疫吸附试验（ELISA）检测细胞培养上清液中hlL-1Ra和hlL-10蛋白表达量的水平。结果酶切和测序表明获得了与预期结果一致的PLXRN—IL—IRa和PLXRN—IL-10真核表达载体。稳定转染软骨细胞后，RT-PCR检测到了细胞内hIL-1Ra和hIL-10mRNA片段。ELISA检测发现基因转染组均有相应的一定量的hlL．1Ra和hIL-10表达，单个基因转染组中分别为（60．47±15．13）和（19．73±4．10）ng／L；联合基因转染组为（67．15±11．47）和（16．76±9．96）ng／L。未转染组及PLXRN空质粒转染组均无hIL—IRa和hlL-10表达，基因转染组与对照组比较差异有统计学意义（P〈0．05），而单个基因转染组和联合基因转染组组间差异无统计学意义（P〉0．05）。结论逆转录病毒载体PLXRN介导的hlL-1Ra和hlL-10联合基因可有效地感染人OA关节软骨细胞并获得稳定表达，为将表达hIL-IRa和hlL-10目的基因的人OA软骨细胞用于OA基因治疗提供了依据。     

Increased superoxide anion release from chondrocytes in response to interleukin 1 and interferons.

In order to investigate a possible mechanism of degradation of cartilage matrix in chronic inflammation, superoxide anion (O2-) release from chondrocytes after stimulation with interleukin 1 (IL 1) and interferons (IFNs) has been studied. Both of these cytokines enhanced O2- release in a dose- and time-dependent fashion. Increased of the O2- release by these cytokines inactivated by heat or acid pretreatment was not observed. These results suggest that the cytokines released in the process of local immune reactions can stimulate the chondrocytes to promote generation and release of O2-. Released O2- may be associated with degradation of cartilage matrix by chondrocytes themselves activated in the process of chronic arthritis.     

Effect of vitamin D metabolites on the expression of alkaline phosphatase activity by epiphyseal hypertrophic chondrocytes in primary cell culture

The effects of three vitamin D3 metabolites, 25-hydroxyvitamin D3 (25-(OH)D3), 1 alpha,25-dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3), and 24R,25-dihydroxyvitamin D3 (24R,25-(OH)2D3) on the activity of alkaline phosphatase (AP), a key enzyme involved in biomineralization, have been studied in primary cultures of chicken epiphyseal growth plate chondrocytes. Dosages of 1 alpha, 25-(OH)2D3 (10(-12) to 10(-7) M) caused a progressive, dosage- and time-dependent decrease in cellular AP levels, IC50 occurring at approximately 10(-12) M. In contrast, 24R,25-(OH)2D3 at 10(-13) to 10(-10) M stimulated cellular AP activity, half-maximal stimulation occurring at about 10(-13) M. At higher levels (10(-10) to 10(-7) M), 24R,25-(OH)2D3 caused progressive reduction in AP activity. Maximal effects of 24R,25-(OH)2D3 were evident 48 h after administration of the metabolite. 25-(OH)D3 initially (24 h) caused a weak, dosage-dependent decrease in cellular AP activity, but after 48-72 h, low levels (10(-13) to 10(-11) M) caused a dosage-dependent increase in AP activity. Higher levels of 25-(OH)D (greater than 10(-10) M) were clearly inhibitory to AP. These findings reveal that the AP activity of growth plate chondrocytes is exquisitely sensitive to both 1 alpha,25- and 24R,25-(OH)2D3 but the response to each is in opposite directions. The paradoxical response of the cells to 25-(OH)D3 can be explained if the metabolite is slowly metabolized by a 24-hydroxylase to 24R,25-(OH)2D3 leading to stimulation of cellular AP.(ABSTRACT TRUNCATED AT 250 WORDS)     

1α,25-Dihydroxyvitamin D3 receptors and their action in embryonic chick chondrocytes

Summary The role of vitamin D in the maturation of epiphyseal chondrocytes was investigated in the developing chick embryo. Cartilage tissues were divided into two parts: resting cartilage and growth cartilage. A cytosol component to which 1α,25-dihydroxyvitamin D₃ (1α,25(OH)₂D₃) is specifically bound first appeared in the growth cartilage on day 15, rapidly increased, and attained a maximum on day 19. The calcium content of the growth cartilage also began to increase on day 15 and continued to increase in parallel with the 1α,25(OH)₂D₃ receptor levels. Glycosaminoglycan (GAG) synthesis by the growth cartilage cells increased from day 11–17 and rapidly declined thereafter reciprocally with the increase in calcium and receptor levels. In the resting cartilage, no cytosol receptor for 1α,25(OH)₂D₃ was detected up to hatching time. The calcium content and GAG synthesis in the resting cartilage were very low and did not change appreciably throughout development. No receptor-like macromolecule for 24R,25-dihydroxyvitamin D₃ (24R,25(OH)₂D₃) was recognized in either the resting or growth cartilage. 1α,25(OH)₂D₃ added to the culture of chondrocytes from the epiphyseal growth cartilage inhibited GAG synthesis and stimulated its release from the cell layer into the medium in a dose-dependent manner. Thesein vitro effects of 1α,25(OH)₂D₃ were not observed in chondrocytes obtained from 13-day-old growth cartilage and 19-day-old resting cartilage. 25-Hydroxyvitamin D₃ and 24R,25(OH)₂D₃ had no effect on chondrocytes in any of the preparations. These results suggest that 1α,25(OH)₂D₃ is directly involved in the maturation of chondrocytes and possibly in the calcification of growth cartilage.     

Sensitivity of anulus fibrosus cells to interleukin 1 beta. Comparison with articular chondrocytes

STUDY DESIGN: Anulus fibrosus cells from rabbits were grown in primary culture 1) to study their ability to produce prostaglandin E2 and Type II phospholipase A2, and to express stromelysin-1 messenger ribonucleic acid; and 2) to study the effect of interleukin 1 beta on this production and on proteoglycan aggregation. OBJECTIVES: To investigate the potency of anulus fibrosus cells to respond to interleukin 1 beta by producing degradative and inflammatory agents as compared with the potency of articular chondrocytes in the same animal. SUMMARY OF BACKGROUND DATA: Interleukin 1 beta has been implicated in the degradation of intervertebral discs. The way anulus fibrosus cells differ from articular chondrocytes in their responses to interleukin 1 beta remains to be established. METHODS: Anulus fibrosus cells and articular chondrocytes were obtained from young rabbits, grown in primary culture, and incubated with interleukin 1 beta. The newly synthesized proteoglycan was measured by labeling with [35S]-sulfate. Proteoglycan aggregation was analyzed by the elution profile on Sepharose 2B columns. The contents of collagen Type II and stromelysin-1 messenger ribonucleic acid were assessed by Northern blot analysis. The Type II phospholipase A2 activity was measured using a fluorometric substrate. Prostaglandin E2 production was evaluated by radioimmunoassay. RESULTS: Anulus fibrosus cells had 2.5-fold less Type II collagen messenger ribonucleic acid than articular chondrocytes, and interleukin 1 beta had no significant effect on this. Anulus fibrosus cells synthesized and secreted four-fold less proteoglycan than articular chondrocytes. Interleukin 1 beta reduced the anulus fibrosus content of total [35S]-sulfated proteoglycan by 35% (P < 0.01), and that of articular cells by 41% and decreased proteoglycan aggregation. Interleukin 1 beta induced the production of stromelysin-1 messenger ribonucleic acid in both cell types. The stromelysin-1 messenger ribonucleic acid content of anulus fibrosus cells was one half that of articular cells. Interleukin 1 beta increased the production of prostaglandin E2 and caused a dose-dependent secretion of Type II phospholipase A2 activity in both cell types. Its effect was 2.5-fold lower in anulus fibrosus cells than in articular chondrocytes. CONCLUSION: Anulus fibrosus cells can be stimulated by interleukin 1 beta to produce factors implicated in local degradative and inflammatory processes. This production is associated with decreased proteoglycan aggregation. Anulus fibrosus cells respond slightly less well to interleukin 1 beta in vitro than do articular cells.     

玻璃化冻存对兔关节软骨细胞存活率及代谢活性的影响

目的探索理想的关节软骨细胞低温保存方法。方法分别采用玻璃化冻存法、程序性降温法及梯度降温法对兔关节软骨细胞进行低温保存,通过流式细胞仪计数及阿尔新蓝染色等方法了解复苏后软骨细胞的存活率、凋亡率及生物活性。结果采用玻璃化冻存法保存的软骨细胞存活率为(86.57±1.67)%,明显高于传统的程序性降温法及梯度降温法;玻璃化冻存对软骨细胞合成糖胺多糖的能力有一定影响,但与新鲜未冷冻组相比,差异无统计学意义(P>0.05)。结论玻璃化冻存法较传统的保存方法能显著提高冷冻保存后兔关节软骨细胞的存活率,并能维持细胞的生物活性,是一种理想的软骨细胞低温保存方法。     

磷脂酶D对高糖培养的肾小球系膜细胞骨架的影响

目的 研究高糖环境下肾小球系膜细胞（GMC）内磷脂酶D（PLD）的活性改变及其对细胞骨架的影响。方法 对高糖（30mmol/L)刺激48h的大鼠GMC，用酶联比色法测定磷脂酰胆碱专一性磷脂酶D（PC-PLD）活性，底物磷酸化法检测蛋白激酶C（PKC）的活性。用免疫荧光标记和共聚焦显微镜显示并测量F-actin的表达。结果 高糖刺激48h后，GMC内PC-PLD和PKC活性明显增高，而F-actin荧光表达减少，排列紊乱，给予PC-PLD抑制剂后，高糖培养的GMCPKC活性明显下降。F-actin的荧光表达和排列都得到显著改善。结论 高糖时PLD活性增高可以通过PKC途径影响GMC骨架的组装状态。改变系膜细胞收缩功能。     

吗啡急性处理对脂多糖刺激后离体星形胶质细胞活性的影响

目的　观察不同浓度吗啡急性处理对脂多糖刺激后乳鼠离体星形胶质细胞活性的影响。方法　体外培养星形胶质细胞于融合状态 ,随机分为八组 :对照组 (L0 M0 组 )、0 5 μmol/L吗啡组 (L0 M0 5组 )、1 0 μmol/L吗啡组 (L0 M1 0 组 )、2 0 μmol/L吗啡组 (L0 M2 0 组 )、1 0 μg/ml脂多糖组(L1M0 组 )、1 0 μg/L脂多糖 +0 5 μmol/L吗啡组 (L1M0 5组 )、1 0 μg/ml脂多糖 +1 0 μmol/L吗啡组 (L1M1 0 组 )、1 0 μg/L脂多糖 +2 0 μmol/L吗啡组 (L1M2 0 )。在相应组中加入相应终浓度的吗啡和脂多糖 ,继续培养 2 4h。采用神经胶质纤维酸性蛋白 (GFAP)免疫组化方法分别检测星形胶质细胞免疫活性。结果　L0 M0 5、L0 M1 0 、L0 M2 0 组对正常星形胶质细胞形态均无影响 ;L1M0 组的星形胶质细胞GFAP免疫反应阳性细胞平均光密度 (AOD)明显高于L0 M0 组 (P <0 0 1) ;L1M1 0 和L1M2 0组GFAP阳性产物AOD值比L1M0 组均明显降低 (P <0 0 1)。结论　吗啡的急性镇痛机制可能与其抑制星形胶质细胞激活有关     

Downregulation of protein kinase C and insulin-stimulated 2-deoxyglucose uptake in rat adipocytes by phorbol esters, glucose, and insulin

Phorbol esters translocatively activate and subsequently downregulate protein kinase C and insulin-stimulated glucose uptake in rat adipocytes. This study examined the possibility that other translocative activators of protein kinase C in rat adipocytes, e.g., insulin and glucose, provoke similar downregulating effects. Pretreatment of rat adipocytes for 20-24 h with phorbol esters, 3 nM insulin, 20 mM glucose, or 3 nM insulin plus 20 mM glucose resulted in concomitant decreases in protein kinase C and insulin-stimulated (or phorbol ester-stimulated) [3H]-2-deoxyglucose uptake. Downregulating effects of glucose on protein kinase C and insulin-stimulated [3H]-2-deoxyglucose uptake were also evident within 30 min in adipocytes freshly incubated in medium containing 5-20 mM, rather than 0, glucose. These findings confirm that protein kinase C is required during insulin-stimulated glucose uptake and raise the possibility that downregulation of protein kinase C by continued translocative activation of the enzyme may contribute (along with other factors) to impaired responsiveness of the glucose transport system after prolonged insulin and/or glucose treatment.     

Effects of insulin, contraction, and phorbol esters on mitogen-activated protein kinase signaling in skeletal muscle from lean and ob/ob mice

Effects of diverse stimuli, including insulin, muscle contraction, and phorbol 12-myristate-13-acetate (PMA), were determined on phosphorylation of mitogen-activated protein kinase (MAPK) signaling modules (c-Jun NH(2)-terminal kinase [JNK], p38 MAPK, and extracellular signal-related kinase [ERK1/2]) in skeletal muscle from lean and ob/ob mice. Insulin increased phosphorylation of JNK, p38 MAPK, and ERK1/2 in isolated extensor digitorum longus (EDL) and soleus muscle from lean mice in a time- and dose-dependent manner. Muscle contraction and PMA also elicited robust effects on these parallel MAPK modules. Insulin action on JNK, p38 MAPK, and ERK1/2 phosphorylation was significantly impaired in EDL and soleus muscle from ob/ob mice. In contrast, muscle contraction-mediated JNK, p38 MAPK, and ERK1/2 phosphorylation was preserved. PMA effects on phosphorylation of JNK and ERK1/2 were normal in ob/ob mice, whereas effects on p38 MAPK were abolished. In conclusion, insulin, contraction, and PMA activate MAPK signaling in skeletal muscle. Insulin-mediated responses on MAPK signaling are impaired in skeletal muscle from ob/ob mice, whereas the effect of contraction is generally well preserved. In addition, PMA-induced phosphorylation of JNK and ERK1/2 are preserved, whereas p38 MAPK pathways are impaired in skeletal muscle from ob/ob mice. Thus, appropriate MAPK responses can be elicited in insulin-resistant skeletal muscle via an insulin-independent mechanism.     

阳离子多肽MP-1拮抗内毒素/脂多糖活性的实验研究

目的　探讨阳离子多肽MP -1对内毒素/脂多糖(LPS)攻击小鼠的作用及机制。方法将30只昆明小鼠随机分为MP- 1组(尾静脉注射3mg/kgMP- 1)、致伤组(尾静脉注射20mg/kgLPS)、保护组(先注射20mg/kgLPS, 20s内再注射3mg/kgMP- 1),每组10只。观察3组小鼠注射后3d内的存活情况。应用生物传感器及FASTfit作图,比较MP- 1、多黏菌素(PMB)与LPS的亲和力,以Kd值表示。通过动态比浊法和鲎试验定量,比较5、10、20、40μmol/LMP -1、PMB对2μg/LLPS的中和作用,以LPS中和0μmol/LMP -1、PMB为对照。采用逆转录聚合酶链反应法,观察MP- 1对LPS刺激的10只昆明小鼠腹腔巨噬细胞(PM)Toll样受体4(TLR4)mRNA、肿瘤坏死因子(TNF)αmRNA、白细胞介素(IL)6mRNA表达的影响。　结果　致伤组小鼠注射LPS后48h全部死亡。保护组小鼠精神状态一度萎靡但恢复较快,食欲、活动度在短时间内改善,存活率为90%。MP- 1组小鼠存活率为100%。MP -1对LPS具有高亲和力(Kd值为484. 0nmol/L)但弱于对LPS有极高亲和力的PMB(Kd值为18.9nmol/L). MP- 1具有中和LPS的能力但弱于PMB; 20、40μmol/LMP -1中和LPS的能力明显高于0μmol/LMP- 1(P<0. 01).MP- 1对LPS刺激的小鼠PM-TLR4mRNA、TNF- αmRNA和IL -6mRNA的表达均有显著的抑制作用。　结论　MP -1对L     

异搏定对急性胰腺炎大鼠磷脂酶A2影响的研究

目的探讨急性胰腺炎(AP)时胰组织磷脂酶A2(PLA2)的变化,以及钙通道阻滞剂异搏定对其的治疗作用.方法采用"十二指肠闭袢法”诱发AP大鼠模型,随机分组,观测AP组和异搏定治疗组PAL2活性变化,同期行胰腺组织进行光镜和电镜检查.结果诱发AP16h和24h,异搏定治疗组胰腺组织PLA2活性(32.34±3.87,35.26±4.52)较AP组(44.83±5.31,47.77±5.86)明显降低(P<0.01),病理改变明显减轻.结论大鼠AP时存在PLA2的活化,钙通道阻滞剂异搏定可通过抑制PLA2的活化而起到治疗AP的良好作用.     

Effect of calcium, vitamins K1 and D3 on bone in galactosemia

Classical galactosemia is an inherited disorder of galactose metabolism. Recently, diminished bone mineral content (BMC) in children and adolescents has been found. The aim of this study was to evaluate the effect of calcium, vitamins K(1) and D(3) supplementation on bone in children with galactosemia. A 2-year randomized, double-blind, placebo-controlled clinical trial was undertaken in which 40 children with classical galactosemia (13 males and 27 females, aged 3-17 years) were included to receive daily either 750 mg calcium, 1.0 mg vitamin K(1) and 10.0 microg vitamin D(3) or placebo. BMC of femoral neck, lumbar spine and total body and body composition data were determined by dual energy X-ray absorptiometry (DXA) at baseline and after 1 and 2 years. Diet was assessed using a food frequency questionnaire and a 3-day food diary. Biochemical measurements were determined at baseline and after 1 and 2 years. In the children receiving treatment, carboxylated osteocalcin (cOC) concentration significantly increased (P < 0.001) and undercarboxylated osteocalcin (ucOC) concentration significantly decreased (P = 0.001) when compared to the children receiving placebo. Furthermore, there was a statistically significant increase in BMC of lumbar spine (P = 0.001), lean tissue mass (LTM: P = 0.016) and fat mass (FM: P = 0.014) in the treatment group when compared to the placebo group. The significant increase in cOC and decrease in ucOC concentration in the treatment group were present in prepubertal (P < 0.001 and P = 0.006 respectively) and pubertal children (P = 0.004 and P = 0.042 respectively). The significant increase in BMC of lumbar spine in the treatment group was present only in the prepubertal children (P = 0.015). Supplementation of calcium, vitamins K(1) and D(3) given in this dose (750 mg, 1.0 mg and 10.0 mug respectively) is likely to have a role in the treatment of BMC abnormalities in galactosemia.     

Effects of phorbol esters and pertussis toxin on calcitonin-stimulated accumulation of cyclic AMP in neonatal mouse calvarial bones

Summary Calcitonin (CT) is a well-known inhibitor of osteoclastic bone resorption bothin vivo andin vitro. The effect is mediated by activation of adenylate cyclase and subsequent increased levels of cyclic AMP (cAMP). We report here that CT-induced (30 nmol/liter) accumulation of cAMP in cultured neonatal mouse calvaria is enhanced two-fold by 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nmol/liter) and phorbol 12,13-dibutyrate (PDBU; 100 nmol/liter), two protein kinase C (PKC)-activating phorbol esters, whereas phorbol 13-monoacetate (phorb-13; 100 nmol/liter), a related compound that does not activate PKC, has no effect. The ability of TPA and PDBU to enhance CT-stimulated cAMP accumulation was obtained also in the presence of indomethacin (1 μmol/liter). Kinetic studies revealed that TPA enhanced the cAMP response to CT at all the time points at which CT had a significant effect per se and that TPA did not alter the time-course of the cAMP response to CT. Treatment with pertussis toxin (100 ng/ml) enhanced cAMP response to parathyroid hormone (10 nmol/liter) and prostaglandin E₂, but not to CT. From these data it is concluded that PKC, but not pertussis toxin-sensitive guanyl nucleotide-binding proteins (G-proteins), can interact with and modify the signal transducing system for CT in osteoclasts.     

脂多糖对小鼠肺成纤维细胞Thy-1 mRNA表达的影响

目的 评价脂多糖(LPS)对小鼠肺成纤维细胞胸腺细胞分化抗原-1(Thy-1)mRNA表达的影响.方法 原代培养小鼠肺成纤维细胞接种于96孔培养板密度(1×104/ml).培养48 h后,将其分为4组(n=3):PBS对照组(C组)、0.01 μg/ml LPS组(LPS0.01组)、0.10 μg/ml LPS组(LPS0.10组)和1.00μg/ml LPS组(LPS1.00组),分别加入PBS或以上终浓度LPS,在加入后即刻、6、24、48和72 h时(T0-4),分别采用CCK-8细胞计数法检测细胞增殖水平,RT-PCR法检测细胞Thy-1 mRNA表达.结果 与C组相比,T3,4时其余组细胞增殖水平升高,Thy-1 mRNA表达下调(P＜0.05);T3,4时LPS0.01组、LPS0.10组和LPS1.00组细胞增殖水平依次升高,Thy-1 mRNA表达依次下调(P＜0.05).结论 LPS可下调Thy-1 mRNA表达,引起小鼠肺成纤维细胞异常增殖,提示内毒素血症诱发肺纤维化与肺成纤维细胞Thy-1表达下调有关.     

Effect of interleukin 1 beta on osteoblastic clone MC3T3-E1 cells

Summary The effect of recombinant interleukin 1 Beta (IL-1(β)) was investigated on osteoblastic cell line MC3T3-E1 cloned from mouse calvaria. IL-1(β) stimulated cell proliferation which increased cell number and caused dose-related stimulation of DNA synthesis, with a maximal effect at a concentration of 12.5 U/ml; suppressed alkaline phosphatase activity and collagen synthesis maximally at 0.5 and 62.5 U/ml, respectively; and increased the amount of free [³H] hydroxyproline in the cultures, but the amount was quite low. Prostaglandin E₂ synthesis was also stimulated dose dependently by the presence of IL-1(β), with a maximal increase at 2.5 U/ml, at which concentration the prostaglandin E₂ level in the medium was 1.61±0.10 ng/ml. The increased prostaglandin E₂ synthesis did not affect either the IL-1(β)-mediated change in DNA or collagen synthesis or alkaline phosphatase activity. These results extend the possibility that IL-1(β) is to act as a regulator of bone formation.