Endothelin-1 (ET-1) promotes a proinflammatory microglia phenotype in diabetic conditions

Diabetes increases the risk and severity of cognitive impairment, especially after ischemic stroke. It is also known that the activation of the endothelin (ET) system is associated with cognitive impairment and microglia around the periinfarct area produce ET-1. However, little is known about the effect of ET-1 on microglial polarization, especially under diabetic conditions. We hypothesized that (i) ET-1 activates microglia to the proinflammatory M-1-like phenotype and (ii) hypoxia/ lipopolysaccharide (LPS) activates the microglial ET system and promotes microglial activation towards the M-1 phenotype in diabetic conditions. Microglial cells (C8B4) cultured under normal-glucose (25 mmol/L) conditions and diabetes-mimicking high-glucose (50 mmol/L) conditions for 48 h were stimulated with ET-1, cobalt chloride (200 μmol/L), or LPS (100 ng/mL) for 24 h. PPET-1, ET receptor subtypes, and M1/M2 marker gene mRNA expression were measured by RT-PCR. Secreted ET-1 was measured by ELISA. A high dose of ET-1 (1 μmol/L) increases the mRNA levels of ET receptors and activates the microglia towards the M1 phenotype. Hypoxia or LPS activates the ET system in microglial cells and shifts the microglia towards the M1 phenotype in diabetic conditions. These in vitro observations warrant further investigation into the role of ET-1-mediated activation of proinflammatory microglia in post-stroke cognitive impairment in diabetes.

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Homologous and heterologous in vitro regulation of pig pituitary somatostatin receptor subtypes, sst1, sst2 and sst5 mRNA

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0320437 ◽

2004 ◽

Vol 32 (2) ◽

pp. 437-448 ◽

Cited By ~ 15

Author(s):

RM Luque ◽

S Park ◽

XD Peng ◽

E Delgado ◽

F Gracia-Navarro ◽

...

Keyword(s):

Signaling Pathway ◽

Cell Cultures ◽

Low Dose ◽

Pituitary Cell ◽

Receptor Expression ◽

Receptor Subtype ◽

High Dose ◽

Receptor Subtypes ◽

Mrna Levels

Somatostatin (SRIF) is commonly regarded as an inhibitor of GH release in rodents and humans. However, in pigs, SRIF can stimulate the release of GH at low (picomolar) doses, while inhibiting GHRH-stimulated GH release at high (nanomolar) doses in primary pituitary cell cultures. One possible mechanism by which pig cells respond differently to the actions of SRIF is by differential expression and regulation of SRIF receptor subtypes. As no information is available on the homologous regulation of SRIF receptors in pigs, we examined the acute (4 h) in vitro effects of SRIF on mRNA levels of SRIF receptors sst1, sst2 and sst5 by multiplex RT-PCR. These particular sst subtypes were selected because all three have been implicated in the inhibitory effects of SRIF on GH release in both rodents and humans. At a high dose (10(-7) M), SRIF stimulated the expression of sst1, sst2 and sst5 in pig pituitary cell cultures. At a low dose (10(-13) M), SRIF markedly increased sst1, without affecting sst2 or sst5. Given that our laboratory has shown SRIF at high and low doses stimulates cAMP production in a subpopulation of pig somatotropes, we sought to determine if this signaling pathway may be responsible for the stimulatory effect of SRIF on its own receptor expression. The receptor-independent cAMP activator forskolin elevated sst1 and sst2 mRNA levels but did not affect sst5 expression, suggesting the stimulatory actions of high- and low-dose SRIF on sst1 and high-dose SRIF on sst2 mRNA levels can be mediated by activation of cAMP, whereas the stimulatory effect of high-dose SRIF on sst5 mRNA is elicited by a cAMP-independent pathway. Interestingly, both GHRH (10(-8) M) and ghrelin (10(-6) M), which release GH in pig pituitary cell cultures via cAMP-dependent mechanisms, decreased sst5 without altering sst1 or sst2 mRNA levels. Since the actions of GHRH and ghrelin on sst expression markedly contrasted with that observed for SRIF and forskolin these results clearly indicate GHRH and ghrelin are regulating sst5 mRNA levels by a cAMP-independent signaling pathway. Taken together, our results demonstrate that expression of pig SRIF receptors is under a complex, receptor subtype-selective regulation, wherein the concerted actions of key regulators of somatotrope function would play divergent and dose-dependent effects.

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Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice

Biological Research ◽

10.1186/s40659-020-00316-0 ◽

2020 ◽

Vol 53 (1) ◽

Author(s):

Jintao Gao ◽

Fangru Chen ◽

Huanan Fang ◽

Jing Mi ◽

Qi Qi ◽

...

Keyword(s):

Skin Lesion ◽

Inflammatory Response ◽

Mouse Model ◽

Nuclear Translocation ◽

Marker Gene ◽

Inflammatory Factors ◽

Mrna Levels ◽

Hacat Keratinocytes ◽

Tnf Α

Abstract Background Psoriasis is a common chronic inflammatory skin disease. Keratinocytes hyperproliferation and excessive inflammatory response contribute to psoriasis pathogenesis. The agents able to attenuate keratinocytes hyperproliferation and excessive inflammatory response are considered to be potentially useful for psoriasis treatment. Daphnetin exhibits broad bioactivities including anti-proliferation and anti-inflammatory. This study aims to evaluate the anti-psoriatic potential of daphnetin in vitro and in vivo, and explore underlying mechanisms. Methods HaCaT keratinocytes was stimulated with the mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish psoriatic keratinocyte model in vitro. Cell viability was measured using Cell Counting Kit-8 (CCK-8). Quantitative Real-Time PCR (qRT-PCR) was performed to measure the mRNA levels of hyperproliferative marker gene keratin 6 (KRT6), differentiation marker gene keratin 1 (KRT1) and inflammatory factors IL-1β, IL-6, IL-8, TNF-α, IL-23A and MCP-1. Western blotting was used to detect the protein levels of p65 and p-p65. Indirect immunofluorescence assay (IFA) was carried out to detect p65 nuclear translocation. Imiquimod (IMQ) was used to construct psoriasis-like mouse model. Psoriasis severity (erythema, scaling) was scored based on Psoriasis Area Severity Index (PASI). Hematoxylin and eosin (H&E) staining was performed to examine histological change in skin lesion. The expression of inflammatory factors including IL-6, TNF-α, IL-23A and IL-17A in skin lesion was measured by qRT-PCR. Results Daphnetin attenuated M5-induced hyperproliferation in HaCaT keratinocytes. M5 stimulation significantly upregulated mRNA levels of IL-1β, IL-6, IL-8, TNF-α, IL-23A and MCP-1. However, daphnetin treatment partially attenuated the upregulation of those inflammatory cytokines. Daphnetin was found to be able to inhibit p65 phosphorylation and nuclear translocation in HaCaT keratinocytes. In addition, daphnetin significantly ameliorate the severity of skin lesion (erythema, scaling and epidermal thickness, inflammatory cell infiltration) in IMQ-induced psoriasis-like mouse model. Daphnetin treatment attenuated IMQ-induced upregulation of inflammatory cytokines including IL-6, IL-23A and IL-17A in skin lesion of mice. Conclusions Daphnetin was able to attenuate proliferation and inflammatory response induced by M5 in HaCaT keratinocytes through suppression of NF-κB signaling pathway. Daphnetin could ameliorate the severity of skin lesion and improve inflammation status in IMQ-induced psoriasis-like mouse model. Daphnetin could be an attractive candidate for future development as an anti-psoriatic agent.

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MicroRNA-195 Prevents Hippocampal Microglial Polarization Towards The M1 Phenotype Induced By Chronic Brain Hypoperfusion Through Regulating CX3CL1/CX3CR1 Signalling

10.21203/rs.3.rs-25459/v1 ◽

2020 ◽

Author(s):

Meng Mao ◽

Yi Xu ◽

Xin-Yu Zhang ◽

Lin Yang ◽

Xiao-bin An ◽

...

Keyword(s):

Culture System ◽

Molecular Mechanisms ◽

Immunofluorescence Staining ◽

Neonatal Rat ◽

Injection Technique ◽

Microglial Polarization ◽

Bv2 Cells ◽

Bilateral Carotid ◽

M1 Phenotype

Abstract Background Microglial polarization was found respond dynamically to acute brain hypoxia induced by stroke and traumatic brain injury (TBI). However, studies on the process of microglial polarization during chronic cerebral ischaemia (CCI) are limited. Our goal is to investigate the influence of CCI on microglial polarization following chronic brain hypoperfusion (CBH) and exploit potential molecular mechanisms.Methods CBH model was performed by bilateral carotid artery ligation (2VO) in rats. Using stereotaxic injection technique, lenti-pre-miR-195 and anti-miR-195 oligonucleotide fragments (lenti-pre-AMO-195) were injeted into CA1 region of the hippocampus to construct animal models with high or low expression of miR-195. Immunofluorescence staining and flow cytometry were conducted to examine the status of microglial polarization. In vitro, Transwell co-culture system was taken to investigate the role of miR-195 on neuronal-microglial communication through CX3CL1-CX3CR1 signalling. Quantitative real-time PCR was used to detect the level of miR-195 and inflammatory factors. The protein levels of CX3CL1 and CX3CR1 were evaluated by both western blot and immunofluorescence staining.Results CBH induced by 2VO initiated microglial activation in the rat hippocampus from 1 week to 8 weeks, as evaluated by increased Iba-1 immunofluorescence, that the balance between microglial polarization towards the M1 and M2 phenotypes was shifted towards the M1 phenotype and that the expression of CX3CL1 and CX3CR1 was increased at 8 w following CBH. An in vitro study in a Transwell co-culture system demonstrated that transfection of either primary cultured neonatal rat neurons (NRNs) or microglial BV2 cells with AMO-195 induced M1 polarization of BV2 cells and increased CX3CL1 and CX3CR1 expression and that these effects were reversed by miR-195 mimics. Furthermore, overexpression of miR-195 induced by lenti-pre-miR-195 prevented the changes triggered by knockdown of endogenous miR-195 induced by lentiviral vector-mediated expression of lenti-pre-AMO-195 and 2VO surgery.Conclusions Our findings conclude that downregulation of miR-195 in the hippocampus is involved in CBH-induced microglial polarization towards M1 phenotype by governing communication between neurons and microglia through the regulation of CX3CL1 and CX3CR1 signalling. This indicates that miR-195 may provide a new strategy for clinical prevention and treatment of CBH.

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Olanzapine inhibits hepatic apolipoprotein A5 secretion inducing hypertriglyceridemia in schizophrenia patients and mice

10.1101/2021.02.26.21252514 ◽

2021 ◽

Author(s):

Xiansheng Huang ◽

Yiqi Zhang ◽

Wenqiang Zhu ◽

Piaopiao Huang ◽

Jingmei Xiao ◽

...

Keyword(s):

Mrna Expression ◽

Plasma Triglyceride ◽

High Dose ◽

Mrna Levels ◽

Apolipoprotein A5 ◽

Protein Levels ◽

Olanzapine Treatment ◽

Primary Mouse

Olanzapine, an antipsychotic drug, was reported to induce hypertriglyceridemia, whereas the underlying mechanism remains incompletely understood. This study was to determine the role of apolipoprotein A5 (apoA5) in olanzapine-induced hypertriglyceridemia. In this study, 36 drug-naive and first-episode schizophrenic adult patients (aged 18-60 years) in a multi-center clinical trial (ClinicalTrials.gov NCT03451734) were enrolled. Before and after olanzapine treatment, plasma lipid and apoA5 levels were detected. Moreover, 21 female C57BL/6 J mice (8 weeks old) were divided into 3 groups (n = 7/each group): low-dose olanzapine (3 mg/kg/day), high-dose olanzapine (6 mg/kg/day) and control group. After 6 weeks, plasma glucose, lipids and apoA5 as well as hepatic apoA5 protein and mRNA expression in these animals were detected. In our study in vitro, primary mouse hepatocytes and HepG2 cells were treated with olanzapine of 25, 50, 100 μmol/L, respectively. After 24 hours, apoA5 protein and mRNA levels in hepatocytes were detected. Our study showed that olanzapine treatment significantly increased plasma triglyceride levels and decreased plasma apoA5 levels in these schizophrenic patients. A significant negative correlation was indicated between plasma triglyceride and apoA5 levels in these patients. Consistently, olanzapine dose-dependently increased plasma triglyceride levels and decreased plasma apoA5 levels in mice. Surprisingly, an elevation of hepatic apoA5 protein levels was detected in mice after olanzapine treatment, with no changes of APOA5 mRNA expression. Likewise, olanzapine increased apoA5 protein levels in hepatocytes in vitro, without changes of hepatocyte APOA5 mRNA. Therefore, our study provides the first evidence about the role of apoA5 in olanzapine-induced hypertriglyceridemia. Furthermore, plasma apoA5 reduction, resulting in hypertriglyceridemia, could be attributed to olanzapine-induced inhibition of hepatic apoA5 secretion.

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The biphasic modulation of inhibin mRNA levels and secretion by PMSG in rat granulosa cells in vitro

Reproduction Fertility and Development ◽

10.1071/rd9910215 ◽

1991 ◽

Vol 3 (2) ◽

pp. 215 ◽

Cited By ~ 4

Author(s):

U Michel ◽

Z Krozowski ◽

J McMaster ◽

JH Yu ◽

JK Findlay

Keyword(s):

Steady State ◽

Granulosa Cells ◽

Mrna Level ◽

High Dose ◽

Mrna Levels ◽

High Concentration ◽

A Subunit ◽

High Doses ◽

Vitro Effect

Granulosa cell cultures derived from diethylstilboestrol-treated immature rats were used to study the in vitro effect of pregnant mare serum gonadotrophin (PMSG) on steady state mRNA levels for the inhibin alpha and beta A subunits and the secretion of immunoreactive inhibin and progesterone. After 48 h treatment the dose-response curve of PMSG revealed a maximum stimulation (2.5-3.5 fold) of cytosolic alpha and beta A mRNAs over the range of 1 to 10 mU PMSG mL-1, with corresponding stimulation of inhibin secretion. A high dose of PMSG (160-500 mU mL-1) clearly suppressed inhibin alpha mRNA levels as well as inhibin secretion, whereas progesterone (P) was maximally stimulated (up to 600 fold). Although the level of cytosolic inhibin beta A subunit mRNA was also down-regulated by a high concentration of PMSG in the culture medium, the doses required to suppress its mRNA level to less than those of the control varied. These data demonstrate that low doses of follicle stimulating hormone/luteinizing hormone (FSH/LH)-like (PMSG) activity enhances and high doses decrease the steady-state mRNA levels of inhibin in rat granulosa cells in vitro; this biphasic regulation in vitro reflects the differential regulation of inhibin secretion observed during the rat oestrous cycle.

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Melatonin reduces neuroinflammation and improves axonal hypomyelination by modulating M1/M2 microglia polarization via JAK2-STAT3-telomerase pathway in postnatal rats exposed to lipopolysaccharide

10.21203/rs.3.rs-422990/v1 ◽

2021 ◽

Author(s):

Qiuping Zhou ◽

Lanfen Lin ◽

Haiyan Li ◽

Shuqi Jiang ◽

Huifang Wang ◽

...

Keyword(s):

Inflammatory Mediators ◽

Periventricular White Matter ◽

Microglial Polarization ◽

Proinflammatory Mediators ◽

M2 Microglia ◽

Microglia Polarization ◽

M1 Phenotype ◽

Anti Inflammatory ◽

Postnatal Rats

Abstract Microglia activation and associated inflammation are implicated in the periventricular white matter damage (PWMD) in septic postnatal rats. This study investigated whether melatonin would mitigate inflammation and alleviate the axonal hypomyelination in the corpus callosum in septic postnatal rats. We further explored if this might be through modulating microglial polarization from M1 phenotype to M2 through JAK2/STAT3/telomerase pathway. We reported here that melatonin, indeed, not only can it reduce the neurobehavioral disturbances in LPS injected rats, but it can also dampen microglia mediated inflammation. Thus, in LPS + melatonin group, expression of proinflammatory mediators in M1 phenotype microglia was downregulated. As opposed to this, M2 microglia were increased which was accompanied by upregulated expression of anti-inflammatory mediators along with TERT or MT1. In parallel to this was decreased NG2 expression but increased expression of myelin and neurofilament proteins. That melatonin can improve hypomyelination was confirmed by electron microscopy. In vitro in primary microglia stimulated by LPS, melatonin decreased the expression of proinflammatory mediators significantly; but it increased expression of anti-inflammatory mediators. Additionally, the expression levels of p-JAK2 and p-STAT3 were significantly elevated in microglia after melatonin treatment. Remarkably, the melatonin effects on LPS treated microglia was blocked by melatonin receptor, JAK2, STAT3 and telomerase reverse transcriptase inhibitors, respectively. Taken together, it is concluded that melatonin can attenuate PWMD through shifting M1 microglia towards M2 via MT1/JAK2/STAT3/telomerase pathway. The results suggest a new therapeutic strategy whereby melatonin may be adopted to convert microglial polarization that would ultimately contribute to attenuation of PWMD.

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miR-98-5p Alleviated Epithelial-to-Mesenchymal Transition and Renal Fibrosis via Targeting Hmga2 in Diabetic Nephropathy

International Journal of Endocrinology ◽

10.1155/2019/4946181 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Yingchun Zhu ◽

Jiang Xu ◽

Wenxing Liang ◽

Ji Li ◽

Linhong Feng ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Renal Fibrosis ◽

Epithelial To Mesenchymal Transition ◽

Mesangial Cells ◽

Luciferase Reporter ◽

High Dose ◽

Mrna Levels ◽

Mesenchymal Transition

Recently, microRNAs have been recognized as crucial regulators of diabetic nephropathy (DN) development. Epithelial-to-mesenchymal transition (EMT) can play a significant role in tubulointerstitial fibrosis, and it is a hallmark of diabetic nephropathy progression. Nevertheless, the function of miR-98-5p in the modulation of EMT and renal fibrosis during DN remains barely investigated. Hence, identifying the mechanisms of miR-98-5p in regulating EMT and fibrosis is of huge significance. In our present research, decreased miR-98-5p was demonstrated in db/db mice and mice mesangial cells treated with the high dose of glucose. Meanwhile, activated EMT and increased fibrosis was accompanied with the decrease of miR-98-5p in vitro and in vivo. Additionally, to further find out the roles of miR-98-5p in DN development, overexpression of miR-98-5p was applied. Firstly, in vivo investigation exhibited that elevation of miR-98-5p restrained proteinuria, serum creatinine, BUN, the EMT process, and fibrosis. Furthermore, high glucose was able to promote mice mesangial cell proliferation, EMT process, and induced renal fibrosis, which could be prevented by overexpression of miR-98-5p. Moreover, high mobility group A (HMGA2) can exhibit an important role in diverse biological processes. Here, HMGA2 was investigated as a target of miR-98-5p currently. Luciferase reporter assay was conducted and the correlation of miR-98-5p and HMGA2 was validated. Moreover, it was displayed that HMGA2 was remarkably elevated in db/db mice and mice mesangial cells. Furthermore, miR-98-5p strongly depressed HMGA2 protein and mRNA levels in mice mesangial cells. Overall, these revealed miR-98-5p could suppress the EMT process and renal fibrosis through targeting HMGA2 in DN.

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Diethyl Succinate Modulates Microglial Polarization and Activation by Reducing Mitochondrial Fission and Cellular ROS

Metabolites ◽

10.3390/metabo11120854 ◽

2021 ◽

Vol 11 (12) ◽

pp. 854

Author(s):

Lixiang Wang ◽

Yanli Zhang ◽

Magdalena Kiprowska ◽

Yuqi Guo ◽

Ken Yamamoto ◽

...

Keyword(s):

Tricarboxylic Acid Cycle ◽

Mitochondrial Fission ◽

Protective Role ◽

Microglial Cells ◽

Mitochondrial Activity ◽

Primary Microglia ◽

Microglial Polarization ◽

Diethyl Succinate ◽

M1 Phenotype

Succinate is a metabolite in the tricarboxylic acid cycle (TCA) which plays a central role in mitochondrial activity. Excess succinate is known to be transported out of the cytosol, where it activates a succinate receptor (SUCNR1) to enhance inflammation through macrophages in various contexts. In addition, the intracellular role of succinate beyond an intermediate metabolite and prior to its extracellular release is also important to the polarization of macrophages. However, the role of succinate in microglial cells has not been characterized. Lipopolysaccharide (LPS) stimulates the elevation of intracellular succinate levels. To reveal the function of intracellular succinate associated with LPS-stimulated inflammatory response in microglial cells, we assessed the levels of ROS, cytokine production and mitochondrial fission in the primary microglia pretreated with cell-permeable diethyl succinate mimicking increased intracellular succinate. Our results suggest that elevated intracellular succinate exerts a protective role in the primary microglia by preventing their conversion into the pro-inflammatory M1 phenotype induced by LPS. This protective effect is SUCNR1-independent and mediated by reduced mitochondrial fission and cellular ROS production.

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LncRNA HOXA-AS2 regulates microglial polarization via recruitment of PRC2 and epigenetic modification of PGC-1α expression

Journal of Neuroinflammation ◽

10.1186/s12974-021-02267-z ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Xiaodong Yang ◽

Yi Zhang ◽

Yimeng Chen ◽

Xiaoqin He ◽

Yiwei Qian ◽

...

Keyword(s):

Mononuclear Cells ◽

Epigenetic Modification ◽

Peroxisome Proliferator ◽

Mrna Levels ◽

Peripheral Blood Mononuclear ◽

Microglial Polarization ◽

M2 Polarization ◽

Anti Inflammatory

Abstract Background Microglia-mediated neuroinflammation plays an important role in Parkinson’s disease (PD), and it exerts proinflammatory or anti-inflammatory effects depending on the M1/M2 polarization phenotype. Hence, promoting microglia toward the anti-inflammatory M2 phenotype is a potential therapeutic approach for PD. Long noncoding RNAs (lncRNAs) are crucial in the progression of neurodegenerative diseases, but little is known about their role in microglial polarization in PD. Methods In our study, we profiled the expression of lncRNAs in the peripheral blood mononuclear cells (PBMCs) of PD patients using a microarray. RT-qPCR was used to evaluate the lncRNA levels and mRNA levels of cytokines and microglial cell markers both in vitro and in vivo. RIP and ChIP assays were analyzed for the underlying mechanism of lncRNA regulating microglial polarization. Results We found that HOXA-AS2 was upregulated in the PBMCs of PD patients and negatively associated with peroxisome proliferator-activated receptor gamma coactivator-1a (PGC-1α) expression. Moreover, HOXA-AS2 knockdown significantly repressed microglial M1 polarization and promoted M2 polarization by regulating PGC-1α expression. Mechanistic investigations demonstrated that HOXA-AS2 could directly interact with polycomb repressive complex 2 (PRC2) and modulate the histone methylation of the promoter of PGC-1α. Conclusions Our findings identify the upregulated lncRNA HOXA-AS2 promotes neuroinflammation by regulating microglial polarization through interacts with the PRC2 complex and epigenetically silencing PGC-1α. HOXA-AS2 may be a potential therapeutic target for microglia-mediated neuroinflammation in patients with PD.

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Serotonin-Exacerbated DSS-Induced Colitis Is Associated with Increase in MMP-3 and MMP-9 Expression in the Mouse Colon

Mediators of Inflammation ◽

10.1155/2016/5359768 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Menglu Chen ◽

Lei Gao ◽

Pan Chen ◽

Dandan Feng ◽

Yalin Jiang ◽

...

Keyword(s):

Mrna Expression ◽

Low Dose ◽

Intestinal Inflammation ◽

Human Neutrophils ◽

High Dose ◽

Mrna Levels ◽

Protein Levels ◽

Mouse Colon ◽

Inflammatory Bowel

Background. 5-HT enhances dextran sulfate sodium- (DSS-) induced colitis and is involved in inflammatory bowel disease (IBD). Matrix metalloproteinases (MMPs) play roles in the process of intestinal inflammation.Aims. To examine whether 5-HT induces MMPs expression in mouse colon to enhance DSS-induced colitis.Materials and Methods. C57BL/6J (B6) mice were treated with either low-dose (1.0 mg/kg) or high-dose (2.0 mg/kg) 5-HT by enema, low-dose (1.0%) or high-dose (2.5%) DSS, or combined low-dose (1.0%) DSS and (1.0 mg/kg) 5-HT. Mouse colitis was analyzed. MMPs and tissue inhibitors of MMPs (TIMPs) mRNA were measured by real-time quantitative RT-PCR in mouse colon and in human Caco-2 cells and neutrophils. MMP-3 and MMP-9 protein levels were quantified from immunohistochemistry (IHC) images of mouse colons.Results. 5-HT exacerbated DSS-induced colitis, low-dose 5-HT induces both MMP-3 and MMP-9, and high-dose 5-HT only increased MMP-3 mRNA expression in mouse colon. Mouse colon MMP-3 and MMP-9 protein levels were also elevated by 5-HT treatment. The MMP-2, TIMP-1, and TIMP-2 mRNA levels were increased in the inflamed colon. 5-HT induced MMP-3 and MMP-9 mRNA expression in Caco-2 and human neutrophils, respectively, in vitro.Conclusion. 5-HT induced MMP-3 and MMP-9 expression in mouse colon; these elevated MMPs may contribute to DSS-induced colitis.

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