Differential regulation of monocyte/macrophage cytokine production by pressure

BACKGROUND: Cytokine production by macrophages is essential for the inflammatory response. Normal human interstitial tissue pressure is 20 to 30 mm Hg, but generally decreases in acute inflammation. METHODS: We compared the effect of 20 mm Hg increased pressure (approximating normal interstitial tissue pressure) with that of ambient pressure (resembling pressure in inflamed tissues) on tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta production by undifferentiated (monocytic) and PMA (phorbol 12-, myristate 13-acetate)-differentiated (macrophage-like) THP-1 cells with or without lipopolysaccharide (LPS) (10 ng/mL). RESULTS: Pressure stimulated spontaneous macrophage TNF-alpha secretion (30.5 +/- 6.3 vs. 49.1 +/- 2.8 pg/mL, P <.02), but not monocyte TNF-alpha secretion. Pressure did not stimulate IL-1beta release. As expected, LPS increased basal cytokine release. After LPS stimulation, pressure still tended to stimulate macrophage TNF-alpha, but inhibited monocyte TNF-alpha secretion (P <.05). In contrast, pressure inhibited IL-1beta release by both LPS-treated monocytes (986 +/- 134 vs. 595 +/- 226 pg/mL, P <.02) and macrophages (3,112 +/- 229 vs. 979 +/- 61 pg/mL, P <.01). CONCLUSIONS: Extracellular pressure may regulate TNF-alpha and IL-1beta secretion differentially by monocytes and macrophages.     

Modulation of Leydig cell testosterone production by secretory products of macrophages

Summary.  Unstimulated macrophages from testes inhibited the production of testosterone by Leydig cells from adult, but not immature, Sprague-Dawley rats (significant after 48 h). Similar results were observed with unstimulated macrophage-conditioned media, suggesting that the observed effect was mediated by one or more secretory products. None of these substances was interleukin-1, since macrophage supernatants tested negative in an interleukin-1α and interleukin-1β sensitive, thymocyte assay. Interleukin-6 was detected by a B cell proliferation assay.
After stimulation by LPS, testicular macrophages enhanced testosterone production by Leydig cells from adult and immature rats. This enhancement was dose-dependent and required low concentrations (but over 2.5%) of conditioned media. Interleukin-1 and interleukin-6 activities were detected in LPS-stimulated macrophage supernatants. Supernatants of LPS-stimulated, human monocytes had similar effects on Leydig cells. They were rich in interleukin-1, interleukin-1 receptor antagonist and interleukin-6.
The present study suggests that, in adult rats, testicular macrophages modulate Leydig cell steroidogenesis by secretory products whose secretion depends on the physiological state of macrophages. The factor or factors responsible for stimulation are not species-specific. The effect cannot be accounted for by variations in the concentration of the above mentioned interleukins in macrophage supernatants.     

Influence of rat testicular macrophages on Leydig cell function in vitro

The influence of co-cultures of rat testicular macrophages and Leydig cells (LC) on LC morphology and steroidogenesis was investigated with and without macrophage stimulation by a bacterial lipopolysaccharide (LPS). LC showed an elongated form in the presence of stimulated testicular macrophages. In the presence of non-stimulated testicular macrophages a significant inhibition of testosterone production was observed (decrease of 33%) from 48 h in co-culture while an increase of 16% was obtained at the same culture time, after stimulation of macrophages by LPS. When LC were treated with testicular macrophage-conditioned media (MCM) obtained from LPS-treated macrophages, they became fusiform and there was stimulation (78%) of steroid production. After human FSH stimulation (1-1000 mIU ml-1), MCM from testicular macrophages was no more effective in enhancing testosterone production by LC than was media from untreated LC. Similar experiments with LPS were conducted with macrophages of peritoneal origin. Peritoneal macrophages stimulated or not by LPS in co-cultures with LC or peritoneal MCM did not significantly modify testosterone production. However, these cells were able to modify LC morphology when LPS-MCM was added to LC-culture medium. The present results suggest strongly that testicular macrophage-LC interactions could be important in the control of LC steroidogenesis.     

Effect of 6-gingerol on pro-inflammatory cytokine production and costimulatory molecule expression in murine peritoneal macrophages

BACKGROUND: Pro-inflammatory cytokines produced primarily by macrophages are key elements in many surgical conditions including sepsis, ischemia-reperfusion injury, and transplant rejection. Herbal products are being used as alternative treatments in such inflammatory conditions. Ginger is known for its ethno-botanical applications as an anti-inflammatory agent. 6-gingerol is one of the active ingredients of ginger that imparts ginger with its anti-inflammatory properties. We hypothesized that the anti-inflammatory effect of 6-gingerol is because of inhibition of macrophage activation, more specifically by an inhibition of pro-inflammatory cytokines and antigen presentation by lipopolysaccharide (LPS) activated macrophages. METHODS: To study the effect of 6-gingerol on pro-inflammatory cytokines, we measured the liberation of TNF-alpha, IL-1beta, and IL-12 by murine peritoneal macrophages exposed to several doses of 6-gingerol in the presence of LPS stimulation. We also studied the effect of 6-gingerol on the cell surface expression of B7.1, B7.2, and MHC II. Finally, we examined the APC function of the 6-gingerol treated macrophages by a primary mixed lymphocyte reaction. RESULTS: 6-gingerol inhibited the production of pro-inflammatory cytokines from LPS stimulated macrophages but had no effect on the LPS-induced expression of B7.1, B7.2, and MHC II. The APC function of LPS stimulated macrophages was also unaffected by 6-gingerol treatment. CONCLUSION: Our data indicate that 6-gingerol selectively inhibits production of pro-inflammatory cytokines from macrophages but does not affect either the APC function or cell surface expression of MHC II and costimulatory molecules. We, thus, provide a mechanistic insight into the anti-inflammatory properties of 6-gingerol that may be useful to treat inflammation without interfering with the antigen presenting function of macrophages.     

Agonist of peroxisome proliferator-activated receptor-gamma, rosiglitazone, reduces renal injury and dysfunction in a murine sepsis model.

BACKGROUND: Agonists of the peroxisome proliferator-activated receptor-gamma may help to regulate inflammation by modulating the production of inflammatory mediators and adhesion molecules. The purpose of this study was to determine the protective effects of rosiglitazone on renal injury in a sepsis model and to explore the mechanism. METHODS: In lipopolysaccharide (LPS)-induced mouse sepsis, we examined the effect of rosiglitazone on LPS-induced overproduction of inflammatory mediators, on the expression of adhesion molecules in renal tubular epithelial cells and on renal function. The mechanism of the protective effect was investigated in vitro using human renal tubular epithelial cells. RESULTS: Rosiglitazone significantly decreased serum tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels during sepsis. The levels of blood urea nitrogen and creatinine were significantly lower in mice pre-treated with rosiglitazone than that in LPS-treated mice. Rosiglitazone reduced the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tubular epithelial cells and interstitium of LPS-treated mice. Pre-treatment with rosiglitazone reduced the infiltration of macrophages/monocytes in renal tissue. In cultured tubular epithelial cells, rosiglitazone significantly decreased the expression of ICAM-1 and VCAM-1 induced by TNF-alpha or IL-1beta, inhibited the degradation of inhibitor kappaBalpha (IkappaBalpha) and blocked the activation of the p65 subunit of nuclear factor (NF)-kappaB. CONCLUSIONS: These results indicate that pre-treatment with rosiglitazone attenuated the production of TNF-alpha and IL-1beta and reduced adhesion molecule expression in renal tubular epithelial cells of LPS-treated mice. Rosiglitazone has an anti-inflammatory effect in renal tubular epithelial cells through the inhibition of NF-kappaB activation.     

Macrophage-mediated cytotoxicity against cultured pancreatic islet cells

Direct macrophage cytotoxicity against islet cells was examined in a morphological and biochemical study using mouse pancreatic islet cell monolayers cultured in the presence of macrophages. Secretory responsiveness of CBA/J beta cells was tested after 4 days of coculture with syngeneic or allogeneic (C57BL/6J) peritoneal macrophages. Although basal secretion of insulin in response to 5.5 mM glucose was not affected, stimulated insulin secretion in response to 16.5 mM glucose and 5 mM theophylline was reduced by as much as 70% in the presence of syngeneic or allogeneic macrophages. No such effect on stimulated insulin release was observed from cultured islets incubated in the presence of macrophage-conditioned medium. After refeeding the cultures at 4 days, zones of islet cell lysis began to appear wherever macrophages came into contact with islet cells. This macrophage-mediated killing was observed regardless of the source of the macrophages (e.g., intraislet "resident" macrophages, thioglycollate-stimulated peritoneal exudate macrophages, bone-marrow-derived macrophages, and splenic macrophages). The killing was seen with both syngeneic and allogeneic macrophages. Macrophages adjacent to islet cells extended filopodia into the monolayers, and those that adhered to the top of the islet cells formed lytic plaques. This study, by providing direct evidence of macrophage cell-mediated killing of islet cells, suggests the value of eliminating resident macrophages prior to islet transplantation into syngeneic or allogeneic hosts.     

Inflammatory cell infiltration around beta 2-microglobulin amyloid deposition: histologic comparison of beta 2-microglobulin amyloidosis with AA or AL amyloidosis]

Thirty-one autopsy cases of beta 2-microglobulin (beta 2M) amyloidosis were pathologically investigated in comparison with 17 autopsy cases of AA or AL amyloidosis. In 20 cases (65%, 20/31) of beta 2M amyloidosis, inflammatory cells, mainly macrophages were seen infiltrating around beta 2M amyloid in intervertebral disks. The more beta 2M amyloidosis advances, the more macrophage infiltration tends to be prominent. In cases of severe beta 2M amyloidosis, the cytoplasm of macrophages around amyloid deposition were swollen with engulfed amyloid substance and were often transforming to foreign body multinucleated giant cells. In addition, granulation tissue was formed with infiltrating macrophages, foreign body multinucleated giant cells, capillary proliferation and fibrosis around beta 2M amyloid deposition. On the other hand, inflammatory cell infiltration around amyloid deposition was scarcely seen in AA or AL amyloidosis. Ultrastructurally, macrophages were abundant in phagocytic vacuoles containing amyloid fibrils. These macrophages were immunohistochemically positive for CD68, IL-1 beta and TNF-alpha. Thus, macrophage infiltration around beta 2M amyloid is thought to be responsible for local pain and tissue destruction of dialysis patients.     

Isolation and culture of testicular macrophages from a seasonally breeding species, Phodopus sungorus. Evidence for functional differences between macrophages from active and regressed testes

We have developed an isolation and cultivation protocol for testicular macrophages from the seasonally breeding Siberian hamster, Phodopus sungorus which allows serum-free culture. Macrophages were isolated from the active testes of adult Phodopus kept in long photoperiod (LD, 18hL:6hD), and from the inactive testes of animals with gonadal regression induced by exposure to a short photoperiod (SD, 6hL;18hD; for 10 weeks). The isolated cells were identified as macrophages by (a) electron microscopy, (b) non-specific phagocytosis, and (c) the presence of Fc-receptors. Treatment of the cultures with oFSH (at 0.5 and 1 micrograms ml-1 for 1 and 4 days) significantly stimulated lactate secretion by testicular macrophages from LD hamsters, as expected from studies in the rat. In marked contrast, oFSH did not affect lactate secretion by testicular macrophages from SD hamsters, or by peritoneal macrophages. To test possible macrophage-Leydig cell interactions, the influence of testicular macrophage-conditioned medium (TM-CM) from FSH-responsive LD macrophage cultures was assessed and compared with the effect of peritoneal macrophage-conditioned medium (PM-CM) on testosterone production by testicular parenchyma from LD hamsters. Unexpectedly, and in contrast to previous reports in rats, testosterone production by testes was inhibited significantly by TM-CM from cultures pretreated with either 0.1 or 0.5 micrograms FSH ml-1. FSH alone stimulated testosterone production (due either to LH contamination or to possible paracrine effects). PM-CM from cultures pretreated with FSH did have an inhibitory effect. It is concluded that: (i) There is indirect evidence for the presence of functional FSH receptors on macrophages from the active testes of Phodopus. (ii) Testicular macrophages from inactive testes of Phodopus are not responsive to FSH, implicating impaired macrophage function in the regressed testes of Phodopus exposed to SD. (iii) Testicular macrophages produce a factor which can inhibit testosterone production by incubated testicular tissue.     

MEK/ERK1/2在LPS抑制NRK-52E肾小管上皮细胞增殖中的作用

【摘要】 目的 探讨脂多糖(LPS)对大鼠NRK-52E肾小管上皮细胞增殖的影响及MEK/ERK1/2信号途径的调节作用。方法 不同剂量LPS按不同时间刺激NRK-52E细胞,并以MEK特异性抑制剂U0126干预。使用cell counting kit-8(cck-8)试剂检测细胞增殖,Western blot检测NRK-52E细胞ERK1/2、Akt蛋白磷酸化水平。结果 LPS在0.001、0.01 mg·L-1作用72 h对NRK-52E细胞增殖无明显影响,在0.1、1.0 mg·L-1抑制NRK-52E细胞增殖;MEK特异性抑制剂U0126显著抑制NRK-52E细胞增殖,其作用在2.5、5、10、20 ?滋M浓度之间无显著差异。U0126预处理加强LPS对NRK-52E细胞增殖的抑制作用。LPS诱导NRK-52E细胞ERK1/2和Akt磷酸化;U0126单独或联合LPS处理NRK-52E细胞72 h阻断ERK1/2蛋白磷酸化,伴有pAkt蛋白水平上调。结论 MEK/ERK1/2可能在LPS抑制NRK-52E细胞增殖的过程中起保护作用。     

Renal microenvironments and macrophage phenotypes determine progression or resolution of renal inflammation and fibrosis

Chronic kidney disease involves renal inflammation, interstitial fibrosis, and tubular and vascular atrophy. Macrophages seem to foster all of these histomorphological abnormalities, but their specific contributions remain controversial. Recruited monocytes differentiate into different tissue macrophage phenotypes, but current classifications are largely based on in vitro studies that do not adequately mirror tissue environments in vivo. To overcome this limitation, we propose to classify tissue macrophages according to their predominant roles in the phases of wound healing tissue environments, that is, inflammation, epithelial healing, mesenchymal healing, and fibrolysis. In this review, we discuss the evidence on respective macrophage phenotypes in renal pathology. This view sheds light on several aspects of renal remodeling in kidney disease: (1) renal infection or cell necrosis induces proinflammatory 'M1' macrophages that exacerbate renal cell damage, (2) uptake of apoptotic cells induces anti-inflammatory 'M2c/suppressor' macrophages that promote epithelial and vascular repair, (3) insufficient vascular and epithelial healing despite abundant growth factor secretion promotes profibrotic 'M2a/wound healing' macrophages that accelerate fibrogenesis, and (4) theoretically, fibrolytic macrophages should exist and await investigation.     

Anti-endotoxin monoclonal antibodies inhibit secretion of tumor necrosis factor-alpha by two distinct mechanisms.

OBJECTIVE: To determine whether monoclonal antibodies (mAbs) directed against lipopolysaccharide (LPS, endotoxin) act by promoting LPS neutralization, LPS uptake by macrophages, or both processes, the authors assessed the effects of these agents on LPS-induced cytokine secretion and cellular uptake of LPS. SUMMARY BACKGROUND DATA: MAbs directed against LPS have been shown to attenuate LPS-induced macrophage tumor necrosis factor-alpha (TNF-alpha) secretion, a process that may contribute to protective capacity. The mechanisms by which this process occurs have not been established. METHODS: MAbs directed against LPS were evaluated in vitro for their capacity to (1) inhibit TNF-alpha secretion, and (2) alter fluorescein isothiocyanate-labeled LPS uptake (employing flow cytometry analysis and fluorescence microscopy) by the macrophage-like cell line RAW 264.7. RESULTS: MAb 8G9, an IgG3 directed against the O-antigen polysaccharide region of Escherichia coli 0111:B4 LPS, significantly reduced LPS-induced TNF-alpha secretion and promoted a more than 40-fold increase in LPS uptake by macrophages. The authors established that this was mediated by a Fc receptor-mediated process because 8G9 F(ab')2 fragments that lack the Fc portion of the IgG molecule were capable of inhibiting TNF-alpha secretion, but did not promote increased LPS uptake to the same degree. Cross-reactive, anti-deep core/lipid A mAb 1B6, an IgG2a, also promoted uptake of E. coli 0111:B4 LPS and O-antigen polysaccharide-deficient E. coli J5 LPS, but only inhibited TNF-alpha secretion induced by E. coli J5 LPS to which it binds most efficiently. MAb 3D10, an IgM also directed against the O-antigen polysaccharide region of E. coli 0111:B4 LPS, inhibited TNF-alpha secretion but did not increase cellular uptake of LPS, presumably acting solely due to LPS neutralization. Polymyxin B, an antibiotic that binds stoichiometrically to the lipid A portion of LPS, inhibited TNF-alpha secretion and prevented cellular LPS uptake. CONCLUSIONS: These results suggest that IgG and IgM anti-LPS mAbs exert protective capacity by extracellular neutralization of LPS, while IgG Fc receptor-mediated cellular uptake also may serve to bypass macrophage activation and TNF-alpha secretion by promoting internalization and intracellular neutralization.     

Macrophages in streptozotocin-induced diabetic nephropathy: potential role in renal fibrosis.

BACKGROUND: Renal fibrosis is central to the progression of diabetic nephropathy; however, the mechanisms responsible for fibroblast and matrix accumulation in this disease are only partially understood. Macrophages accumulate in diabetic kidneys, but it is unknown whether macrophages contribute to renal fibrosis. Therefore, we examined whether macrophage accumulation is associated with the progression of renal injury and fibrosis in type 1 diabetic nephropathy and whether macrophages exposed to the diabetic milieu could promote fibroblast proliferation. METHODS: Kidney macrophages, renal injury and fibrosis were analysed in diabetic C57BL/6J mice at 2, 8, 12 and 18 weeks after streptozotocin injection. Isolated rat bone marrow macrophages were stimulated with diabetic rat serum or carboxymethyllysine (CML)-bovine serum albumin (BSA) to determine whether macrophage-conditioned medium could promote the proliferation of rat renal (NRK-49F) fibroblasts. RESULTS: Progressive injury and fibrosis in diabetic nephropathy was associated with increased numbers of kidney macrophages. Macrophage accumulation in diabetic mice correlated with hyperglycaemia (blood glucose, HbA1c levels), renal injury (albuminuria, plasma creatinine), histological damage and renal fibrosis (myofibroblasts, collagen IV). Culture supernatant derived from bone marrow macrophages incubated with diabetic rat serum or CML-BSA induced proliferation of fibroblasts, which was inhibited by pre-treating fibroblasts with interleukin-1 (IL-1) receptor antagonist or the platelet-derived growth factor (PDGF) receptor kinase inhibitor, STI-571. CONCLUSION: Kidney macrophage accumulation is associated with the progression of renal injury and fibrosis in streptozotocin-induced mouse diabetic nephropathy. Elements of the diabetic milieu can stimulate macrophages to promote fibroblast proliferation via IL-1- and PDGF-dependent pathways which may enhance renal fibrosis.     

Response of human peritoneal mesothelial cells to inflammatory injury is regulated by interleukin-1b and tumor necrosis factor-a

Peritoneal injury is often associated with alterations of the mesothelium, resulting in peritoneal healing and adhesion formation. We analyzed the effects of pro-inflammatory cytokines on cell morphology and proliferation of human peritoneal mesothelial cells (HPMC). After 48 hours, HPMC formed a confluent layer with cell volumes of 2,662+/-111 fL. Treatment of HPMC with interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) induced mesothelial disintegration and alterations in mesothelial cell morphology, which were associated with an interleukin-1beta-triggered increase in cell volume (3,028+/-118 fL; p<0.05) and exfoliation of cells into the supernatants of cell cultures (p<0.05). Whereas TNF-alpha arrested HPMC in the G0/G1 phase (p<0.05), interleukin-1beta caused an increase of cells into the S phase of the cell cycle. In addition, interleukin-1beta and interferon-gamma exerted a proliferative effect on HPMC. These changes were independent from mesothelial Na+/H+ antiporter-1 expression. Our data indicate that the response of HPMC to inflammatory injury is regulated by interleukin-1beta and TNF-alpha reflecting their putative role in peritoneal wound healing and adhesion formation.     

Proximal tubule cells stimulated by lipopolysaccharide inhibit macrophage activation

BACKGROUND: Tubule cells can produce a variety of cytokines, extracellular matrix (ECM) components, and adhesion molecules in vitro and in vivo. It is generally assumed that stimulated tubule cells are proinflammatory and at least partially responsible for interstitial inflammation. However, the overall effect of tubular cells on interstitial cells is unknown. In this study, pro- and anti-inflammatory cytokine production and net effects on macrophages of tubule cells activated by lipopolysaccharide (LPS) were examined. METHODS: Tubule cells stimulated with LPS expressed tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-12, monocyte chemoattractant protein-1 (MCP-1), IL-10, and transforming growth factor-beta (TGF-beta). Conditioned media were collected from confluent monolayers of rat tubule cells stimulated, or not, by LPS for 4 and 18 hours, respectively. Macrophages were cultured with conditioned media and/or LPS (0.5 microg/mL) for 18 hours. RESULTS: TNF-alpha and IL-lbeta mRNA of macrophages stimulated by LPS increased more than fivefold when cultured with control conditioned media from unstimulated tubule cells. Surprisingly, TNF-alpha and IL-lbeta levels of macrophages stimulated by LPS were not increased when cultured with conditioned media from activated tubule cells. Neutralizing antibodies to IL-10 and TGF-beta were used to define the inhibitory component(s) in conditioned medium. Anti-IL-10, but not anti-TGF-beta, abolished partially the inhibitory effects of conditioned media on macrophages. CONCLUSION: Tubule cells produce both pro- and anti-inflammatory cytokines and the net effect, partially explained by IL-10, of tubule cells activated with LPS is to inhibit activity of macrophages. Thus, the net effect of activated tubule cells on interstitial pathology may in certain circumstances, be anti- rather than pro-inflammatory.     

Modulation of interleukin-6 by beta2-adrenoceptor in endotoxin-stimulated renal macrophage cells.

BACKGROUND: Activation of the cAMP signaling pathway by means of beta2-adrenoceptor agonists has been shown to up-regulate interleukin-6 (IL-6) gene expression and to stimulate IL-6 production in macrophage cells. However, whether beta2-adrenoceptor activation can also modify the rate of IL-6 production in macrophage cells activated by the bacterial endotoxins has not yet been determined. Using renal resident macrophage cells treated with endotoxin, lipopolysaccharide (LPS), and beta2-adrenoceptor agonist, terbutaline, we investigated the role of cAMP pathway, tumor necrosis factor (TNF)-alpha and mitogen-activated protein kinase (MAPK) pathway (p42/p44) in regulating IL-6 production. METHODS: IL-6 protein, mRNA, and promoter activity were measured in these cells exposed to LPS (1 microg/ml) and/or terbutaline (10(-9) to 10(-6) M). Furthermore, the time course effects of terbutaline on cAMP, MAPK (p42/p44), and TNF-alpha release were evaluated in the cells. RESULTS: Terbutaline at high concentrations (10(-6) M) significantly up-regulated IL-6 by approximately 25% (P<0.05), whereas at a lower concentration (10(-8) M), it down-regulated IL-6 production by 42% (P<0.05). Terbutaline (10(-8) and 10(-6) M) caused a concentration- and time-dependent stimulation of cAMP (P<0.05) and TNF production (P<0.05) and a time-dependent decrease in MAPK activity (P<0.05). Following the addition of a cAMP inhibitor, IL-6 promoter activity was correlated with TNF-alpha levels and MAPK activity. CONCLUSIONS: A biphasic effect of beta2-adrenoceptor agonist on IL-6 production in renal resident macrophage cells became apparent when LPS was exposed to the cells. The terbutaline-induced down-regulation of IL-6 gene production was mediated by an inhibitory effect of terbutaline on TNF-alpha, which was exerted through the MAPK and cAMP pathways, whereas the up-regulation appeared to be due to a direct action of intracellular cAMP.     

胃癌细胞中miR-455-3p的表达及其对增殖和凋亡的影响

目的:探讨mi R-455-3p在胃癌细胞中的表达及对胃癌细胞增殖和凋亡的影响。方法:用q RT-PCR检测mi R-455-3p在正常胃黏膜上皮细胞RGM-1及5种胃癌细胞系(AGS、Hs746T、MGC-803、SGC-7901及BSG-823)中的表达。将胃癌细胞mi R-455-3p模拟物后,分别用CCK8法检测细胞增殖,流式细胞术检测细胞凋亡,Western blot检测细胞p27 kip1、p21的蛋白表达,分光光度法检测细胞caspase酶活性。结果:mi R-455-3p在5种胃癌细胞系中的表达水平明显低于RGM-1细胞系,其中在AGS细胞中降低最为明显(均P0.05)。AGS细胞转染mi R-455-3p模拟物后,增殖能力明显降低而胞凋亡率明显升高,p27 kip1蛋白表达量明显升高,caspase-3与caspase-9相对活性明显升高(均P0.05),但p21蛋白表达量与caspase-8相对活性无明显改变(均P0.05)。结论:mi R-455-3p在胃癌细胞表达下调,增加其表达可抑制胃癌细胞增殖并促进凋亡,其机制可能与其上调p27 kip1表达及增强caspase-3、caspase-9活性有关。