The Potential Role of Monocyte Chemoattractant Protein-1 for Major Depressive Disorder

The immune hypothesis of major depressive disorder (MDD) fits well with the supposed interaction between genetic and environmental factors in disorders with a complicated etiopathogenesis. It has been suggested that infectious diseases are associated with MDD in that cytokines may play a critical role as a key modulator in the transition between infection and the development of MDD. It has been also suggested that antidepressants have immunomodulatory effects on some cytokines and cytokine receptors, although the exact mechanism has not yet been fully elucidated. Among cytokines, monocyte chemoattractant protein-1 (MCP-1) is especially well known and has attracted considerable interest owing to its immunomodulatory functions. MCP-1 is expressed in highly regionalized neuronal areas in the brain, leading to kind of modulation of neuronal activity and neuroendocrine functions commonly seen in patients with MDD. Additionally, it is involved in the control of other cytokines that have been consistently proposed as associated with the development of MDD. It also has a possible role in the neurodegenerative process of a number of central nervous system (CNS) diseases. Hence, this paper draws from the perspective of immunology to offer several suggestions about the role of MPC-1 in the development of MDD.     

Adrenergic and glucocorticoid modulation of the sterile inflammatory response

Exposure to an intense, acute stressor, in the absence of a pathogen, alters immune function. Exposure to a single bout of inescapable tail shock increases plasma and tissue concentrations of cytokines, chemokines, and the danger associated molecular pattern (DAMP) Hsp72. Although previous studies have demonstrated that adrenergic receptor (ADR) and glucocorticoid receptor (GCR)-mediated pathways alter pathogen or microbial associated molecular pattern (MAMP)-evoked levels of cytokines, chemokines, and Hsp72, far fewer studies have tested the role of these receptors across multiple inflammatory proteins or tissues to elucidate the differences in magnitude of stress-evoked sterile inflammatory responses. The goals of the current study were to (1) compare the sterile inflammatory response in the circulation, liver, spleen, and subcutaneous (SQ) adipose tissue by measuring cytokine, chemokine, and DAMP (Hsp72) responses; and (2) to test the role of alpha-1 (α₁), beta-1 (β₁), beta-2 (β₂), and beta-3 (β₃) ADRs, as well as GCRs in signaling the sterile inflammatory response. The data presented indicate plasma and SQ adipose are significantly more stress responsive than the liver and spleen. Further, administration of ADR and GCR-specific antagonists revealed both similarities and differences in the signaling mechanisms of the sterile inflammatory response in the tissues studied. Finally, given the selective increase in the chemokine monocyte chemotactic protein-1 (MCP-1) in SQ tissue, it may be that SQ adipose is an important site of leukocyte migration, possibly in preparation for infection as a consequence of wounding. The current study helps further our understanding of the tissue-specific differences of the stress-induced sterile inflammatory response.     

Functional characterization of histamine H4 receptor on human mast cells

Among the four different types of histamine receptors (H1-H4), H4R is predominantly expressed in immune cells and involved in immunomodulatory response. Here, in this study we determined the expression of H4R in human mast cells (HMC-1, LAD-2 and primary cord blood derived CD34+ human mast cells) and characterized its functional properties. Interestingly, we found that human mast cells responded to both histamine (natural ligand) and 4-methylhistamine (selective H4R agonist) for sustained intracellular calcium mobilization, degranulation and cytokine production. However, only histamine induced the release of cAMP, but 4-methylhistamine down regulates cAMP indicating that H4R mediates its effect through Gαi/o protein and H1R via Gαq protein. Furthermore, both histamine and 4-methylhistamine induced the production of cysteinyl leukotrienes and LTB4. Using human inflammation antibody array membrane, we found that H4R induced the expression of various inflammatory proteins, involving pro-inflammatory cytokines and chemokines and these are TGF-β1, TNF-α, TNF-β, PDGF-BB, TIMP-2, M-CSF, IP-10, IL-16, IL-6, IL-3, IL-10, MIP-1α, IL-1α, ICAM-1, Eotaxin-2, RANTES, IL-8, MCP-1, and IL-6sR. We also quantified the level of various inflammatory cytokines produced by human mast cells through H4R. It was observed that, the production level of Th2 cytokines IL-4(401.34 pg/ml), IL-5 (64.21 pg/ml) and IL-13 (1044 pg/ml) and classical proinflammatory cytokines IL-6 (221.27 pg/ml) and IL-1β (34.24 pg/ml) and chemokines MCP-1(106 pg/ml) and IL-8 (818.32 pg/ml). Furthermore, activation of H4R caused the phosphorylation of ERK and PI3 K in a time dependent manner. Taken together these data demonstrate that, the activation of H4R in human mast cells produced not only inflammatory mediators that are associated with allergic reactions but also other inflammatory conditions.     

A three-dimensional in vitro model to quantify inflammatory response to biomaterials

In vivo models are the gold standard for predicting the clinical biomaterial–host response due to the scarcity of in vitro model systems that recapitulate physiological settings. However, the simplicity, control and relatively lower cost of in vitro models make them more appropriate to quantify the contribution by each cell, material and molecule within the healing environment. In this study, human fibroblasts and monocytes are co-cultured in a three-dimensional (3-D) tissue model to study foreign body response by observing morphological changes and monitoring inflammatory cytokine production with multiplex quantitative protein analysis. While control monocultures of either cell type alone produced low levels of cytokines, their interactions in co-culture led to morphological changes and increased release of inflammatory cytokines. When challenged with a well-characterized biopolymer, poly(lactic-co-glycolic acid), the co-cultured human cells secreted elevated levels of IL-1β, IL-6, GM-CSF and TNF-α. This 3-D in vitro co-culture model may serve as a building block towards a versatile platform to study mechanisms of material–host interactions by co-culturing cells with engineered phenotypes and reporter systems, or predict patient-specific biocompatibility by using the individual patients’ cells.     

血浆单核细胞趋化蛋白1、可溶性髓系细胞触发受体1及高迁移率族蛋白B1水平对急性肺损伤患者病情及预后的评估价值

目的 探讨血浆单核细胞趋化蛋白1 (MCP-1)、可溶性髓系细胞触发受体1(sTREM-1)及高迁移率族蛋白B1 (HMGB1)水平对急性肺损伤(ALI)患者病情及预后的评估价值.方法 选取2016年1月至2019年12月海口市第三人民医院收治的120例ALI患者,根据ALI患者生存情况分为存活组(78例)和死亡组(4...     

来曲唑联合地塞米松对多囊卵巢综合征患者血清Galectin-3及HSP70的影响

目的 探讨来曲唑联合地塞米松对多囊卵巢综合征(PCOS)患者血清半乳糖凝集素-3(Galectin-3)及热休克蛋白(HSP70)表达的影响。方法 选择2019年6月—2021年6月在我院治疗的PCOS患者220例为研究对象,按随机数表法分为对照组(n=110)和观察组(n=110),对照组常规给予来曲唑治疗。观察组在对照组的基础上加用地塞米松联合治疗。观察并比较两组患者的激素水平,促排卵情况,血清抗苗勒管激素(AMH)、Galectin-3、HSP70及单核细胞趋化蛋白-1(MCP-1)水平及不良反应发生率。结果 治疗后两组患者的性激素水平均改善,且观察组变化幅度高于对照组(P<0.05)。观察组患者雌二醇(E₂)用量低于对照组,成熟卵泡数量和最大卵泡直径均高于对照组(均P<0.05)。两组患者的早期流产率差异无统计学意义(P>0.05);观察组患者的妊娠率高于对照组(P<0.05)。治疗前两组患者AMH、Galectin-3、HSP70、MCP-1水平差异无统计学意义(P>0.05),治疗后两组患者的AMH、Galectin-3、...     

缬沙坦对实验性兔动脉粥样硬化斑块形成的影响

目的 研究缬沙坦对实验性兔动脉粥样硬化血管壁过氧化物酶体增殖物激活受体γ(PPARγ)和单核细胞趋化蛋白-1(MCP-1)的影响.方法 24只新西兰白兔随机分为3组:正常对照组、动脉粥样硬化(AS)造模组、缬沙坦干预组,喂养12周.进行血脂测定、主动脉内膜/中膜比值测定,采用RT-PCR检测PPARγ和MCP-1 mRNA的表达.结果 缬沙坦组血管壁PPARγ mRNA的表达较AS组明显增加(P＜0.05), 缬沙坦组血管壁MCP-1mRNA的表达较AS组明显减少(P＜0.05).血清胆固醇、甘油三酯、低密度脂蛋白胆固醇缬沙坦组与AS组比较均无显著性差异 (P＞0.05), 但均高于对照组(P＜0.01).缬沙坦组内膜/中膜厚度比值较AS组明显减小(P＜0.05).结论 缬沙坦能够抑制血管壁细胞MCP-1的表达, 其具有抗炎作用, 抗炎作用可能与其改善PPARγ表达有关.