Inflammatory and regulatory CCL and CXCL chemokine and cytokine cellular responses in patients with patent Mansonella perstans filariasis

Mansonella perstans (Mp) filariasis is present in large populations in sub-Saharan Africa, and to what extent patent Mp infection modulates the expression of immunity in patients, notably their cellular cytokine and chemokine response profile, remains not well known. We studied the spontaneous and inducible cellular production of chemokines (C-X-C motif) ligand 9 (CXCL9) [monokine induced by interferon (IFN)-γ (MIG)], CXCL-10 [inducible protein (IP)-10], chemokine (C-C motif) ligand 24 (CCL24) (eotaxin-2), CCL22 [macrophage-derived chemokine (MDC)], CCL13 [monocyte chemotactic protein-4 (MCP-4)], CCL18 [pulmonary and activation-regulated chemokine (PARC)], CCL17 [thymus- and activation-regulated chemokine (TARC)] and interleukin (IL)-27 in mansonelliasis patients (Mp-PAT) and mansonelliasis-free controls (CTRL). Freshly isolated peripheral mononuclear blood cells (PBMC) were stimulated with helminth, protozoan and bacterial antigens and mitogen [phytohaemagglutinin (PHA)]. PBMC from Mp-PAT produced spontaneously (without antigen stimulation) significantly higher levels of eotaxin-2, IL-27, IL-8, MCP-4 and MDC than cells from CTRL, while IFN-γ-IP-10 was lower in Mp-PAT. Helminth antigens activated IL-27 and MCP-4 only in CTRL, while Ascaris antigen, Onchocerca antigen, Schistosoma antigen, Entamoeba antigen, Streptococcus antigen, Mycobacteria antigen and PHA stimulated MIG release in CTRL and Mp-PAT. Notably, Entamoeba antigen and PHA strongly depressed (P < 0·0001) eotaxin-2 (CCL24) production in both study groups. Multiple regression analyses disclosed in Mp-PAT and CTRL dissimilar cellular chemokine and cytokine production levels being higher in Mp-PAT for CCL24, IL-27, IL-8, MCP-4, MDC and PARC (for all P < 0·0001), at baseline (P < 0·0001), in response to Entamoeba histolytica strain HM1 antigen (EhAg) (P < 0·0001), Onchocerca volvulus adult worm-derived antigen (OvAg) (P = 0·005), PHA (P < 0·0001) and purified protein derivative (PPD) (P < 0·0001) stimulation. In Mp-PAT with hookworm co-infection, the cellular chemokine production of CXCL10 (IP-10) was diminished. In summary, the chemokine and cytokine responses in Mp-PAT were in general not depressed, PBMC from Mp-PAT produced spontaneously and selectively inducible inflammatory and regulatory chemokines and cytokines at higher levels than CTRL and such diverse and distinctive reactivity supports that patent M. perstans infection will not polarize innate and adaptive cellular immune responsiveness in patients.     

Circulating CCL20: A potential biomarker for active vitiligo together with the number of Th1/17 cells

Background

Vitiligo is an autoimmune disease with varying pathological features. Activation of the CCL20-CCR6 axis plays an important role in chronic inflammatory diseases. However, whether CCL20-CCR6 and Th1/17 cells are indicative of active vitiligo is unclear.

The relationships among monocyte subsets,miRNAs and inflammatory cytokines in patients with acute myocardial infarction

Background

Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.

Low-dose naltrexone inhibits the epithelial-mesenchymal transition of cervical cancer cells in vitro and effects indirectly on tumor-associated macrophages in vivo

The metastasis of cervical cancer has always been a clinical challenge. We investigated the effects of low-dose naltrexone (LDN) on the epithelial mesenchymal transition of cervical cancer cells in vitro as well as its influence on macrophage polarization and associated cytokines in vivo. The results suggested that LDN supressed the proliferation, migration and invasion abilities and promote their apoptosis in Hela cells, whereas the opioid growth factor receptor (OGFr) silenced significantly reversed these effects in vitro. Knockdown the expression of OGFr, the inhibitory of LDN on EMT was weakened. LDN could inhibit cervical cancer progression in nude mice. In additon, LDN indirectly reduced the number of tumor-associated macrophages (TAMs), mainly M2 macrophages, and decreased expression of anti-inflammatory factor IL-10 in the serum of nude mice. These findings demonstrate that LDN could be a potential treatment for cervical cancer.     

趋化因子CCL8与肿瘤发生发展的研究进展

趋化因子CCL8是趋化因子CC家族中的一员，可以在炎症反应和肿瘤免疫等方面发挥重要作用。近来许多研究数据表明，CCL8与人类肿瘤的发生发展密切相关，它在肿瘤微环境中扮演了不可或缺的角色，一方面CCL8可以促进肿瘤细胞的浸润转移，另一方面又可以抑制肿瘤的发生发展。本文主要阐述了目前研究发现的CCL8在肿瘤中的作用，包括肿瘤的发生发展、浸润转移等，以上研究不仅可以帮助我们更加深入的了解肿瘤形成的机制，而且对于寻找更加有效的肿瘤新疗法有着重要的意义。     

Pathogenic implication of epidermal scratch injury in psoriasis and atopic dermatitis

Mechanical scratching, a common external stress affecting the skin, is induced by various causes, such as pruritus. Scratch injury to epidermal keratinocytes upregulates the production and release of chemokine (C-C motif) ligand 20 (CCL20) in vitro, which selectively chemoattracts interleukin (IL)-17A-producing immune cells that express chemokine (C-C motif) receptor 6 (CCR6). In IL-17A-dominant psoriasis, scratch-induced CCL20 upregulation and subsequent accumulation of IL-17A-producing immune cells and CCR6⁺ mature dendritic cells may trigger the development of psoriatic lesions, a process known as the Koebner phenomenon. In IL-4/IL-13-dominant atopic dermatitis, pruritus and subsequent scratching are the primary symptoms. Scratch-induced CCL20 production from keratinocytes may explain why IL-17A levels are also elevated in atopic dermatitis. In contrast, mechanical scratching is likely to negatively regulate IL-13 signaling by upregulating the expression of IL-13 receptor α2, which serves as a decoy receptor for IL-13 in keratinocytes. In this review, we summarize current reports on topics related to the pathogenic role of epidermal scratch injury in psoriasis and atopic dermatitis.     

趋化因子受体CXCR7在结直肠癌组织中的表达及临床意义

[目的]研究家族趋化因子受体7(CXCR7)在人结直肠癌组织中的表达,探讨其表达在结直肠癌发生、发展中的作用。[方法]采用免疫组化染色化学和半定量Western Blot技术检测48例结直肠癌组织和相应的癌旁正常组织标本中CXCR7蛋白的表达,分析其表达与临床病理特征之间的关系。[结果]结直肠癌组织中CXCR7蛋白的表达水平明显高于癌旁正常组织(t=4.974,P0.05)。CXCR7蛋白的表达与结肠直肠癌淋巴结转移、浸润深度和TNM分期有显著相关性。[结论]结直肠癌组织CXCR7蛋白呈高表达,其高表达与结直肠癌的淋巴结转移、分期相关,CXCR7参与了结肠直肠癌的发生、发展。     

miR －7对乳腺癌细胞骨转移的影响

目的：探讨miR－7抑制乳腺癌细胞骨转移的分子机制。方法转染含miR－7基因序列的GFP表达质粒进入MDA－MB－231乳腺癌细胞，荧光显微镜下检测外源基因的整合效率，Western blot方法检测PI3K、AKT－2、CXCR－4和MMP－9的蛋白表达量，Transwell体系检测乳腺癌细胞的迁移能力；建立乳腺癌骨转移模型，病理检查分析骨转移情况；miRNA靶基因预测软件分析miR－7潜在治疗靶点。结果荧光显示含GFP／miR－7基因的质粒被高效转入乳腺癌细胞，转染后癌细胞PI3K、AKT－2和CXCR－4的蛋白量均有明显降低（ P＜0.05， P＜0.01），MMP－9无明显变化（P＞0.05）；体内外模型均显示miR－7可抑制乳腺癌细胞的远位转移；miRNA靶基因预测软件分析显示PI3K是miR－7的潜在沉默靶点之一。结论 miR－7可能通过靶向沉默PI3K／AKT－2通路途径间接影响CXCR－4／SDF－1轴进而抑制乳腺癌细胞的骨转移。     

Biomarkers for evaluation of treatment response in classical Hodgkin lymphoma: comparison of sGalectin‐1, sCD163 and sCD30 with TARC

Soluble Galectin‐1 (sGal‐1, also termed LGALS1), soluble CD163 (sCD163) and soluble CD30 (sCD30) have been reported to be elevated in plasma or serum of patients with classical Hodgkin lymphoma (cHL). We aimed to determine the clinical utility of these biomarkers for evaluation of treatment response compared to thymus and activation regulated chemokine (TARC, also termed CCL17). Plasma or serum samples were prospectively collected among 103 newly diagnosed cHL patients before and after treatment. Levels of sGal‐1, sCD163, sCD30 and TARC were correlated with disease characteristics and clinical treatment response. Elevated plasma levels of sGal‐1, sCD163, sCD30 and TARC were found in 67%, 21%, 91% and 93% of cHL patients respectively. Mean plasma levels of sGal‐1 and sCD30 decreased after treatment but sCD163 did not decrease after treatment. There was no correlation with change of these markers and clinical treatment response in individual patients. TARC levels strongly correlated with disease characteristics and metabolic volume. TARC remained high in 6 out of 7 non‐responsive patients and dramatically decreased in 95 out of 96 responsive patients. In summary, elevated pre‐treatment levels of sGal‐1, sCD163, sCD30 and TARC can be found in patients with cHL. However, only plasma TARC accurately reflects disease activity and correlates with clinical treatment response.