Browsing by Subject "Chemokine"

Now showing 1 - 11 of 11
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    CD26: An expanding role in immune regulation and cancer
    (Murcia : F. Hernández, 2002) Dang, N.H.; Morimoto, C.
    In this review, we highlight major aspects of the biology of CD26, a dipeptidyl peptidase IV (DPPIV)-containing surface glycoprotein with multiple functions. In particular, we discuss findings demonstrating that CD26/DPPIV has an essential role in immune regulation as a T cell activation molecule and a regulator of chemokine function. We also review recent studies that identify key cellular molecules that physically associate with CD26 and the potential consequences of their interaction, including those with clinically-related implications. Furthermore, we present work suggesting a role for CD26 in the pathogenesis and behavior of selected human cancers, both solid tumors and hematological malignancies. We present recent studies that investigate the potential role of CD26 as a molecular target for novel treatment modalities for T cell lymphoid malignancies and possibly other hematological malignancies, with work involving the use of anti-CD26 monoclonal antibody, CD26-transfected cells as well as soluble CD26 molecules.
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    Chemokine CCL14 affected the clinical outcome and correlated with immune infiltrates in thyroid carcinoma
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Zhang, Mi mi; Zhao, Yan dong; Li, Qiang; He, Yue jun
    Background. As an important member of the chemokines, CCL14 plays a vital role in cancer progression. However, the role of CCL14 in THCA has not been investigated. This study aimed to reveal the clinical significance of CCL14 in THCA. Material and Methods. This study evaluated the expression and prognostic value of CCL14 in THCA. Also, the correlation between CCL14 and immune infiltrates was assessed. Enrichment analysis was finally performed to predict CCL14-associated pathways involved in THCA. Results. The mRNA and protein expressions of CCL14 in THCA tissues were down-regulated compared with normal tissues. CCL14 high expression predicted favorable DFI and PFI but did not influence the DSS and OS. Further, CCL14 showed a good prediction performance on the PFI of patients. Enrichment analysis found that CCL14 was negatively correlated with migration-related pathways such as Notch signaling, ECM-receptor interaction, and cell adhesion molecules. Further, we found that CCL14 was negatively related to immune infiltrates and their gene markers. A negative relationship was also observed between CCL14 and immune checkpoint genes. These results implied the potential effect of CCL14 on the immune response and immune therapy in THCA. Conclusions. CCL14 high expression prolonged the DFI and PFI of THCA patients. It was negatively correlated with the migration-related pathways, suggesting that CCL14 might participate in the recurrence of THCA. Further, CCL14 was also shown to be important in immune response and immune therapy in THCA.
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    Chemokines and their receptors in disease
    (Murcia : F. Hernández, 2005) Bendall, L.
    Chemokines are a family of structurally related low molecular weight (8–10 kDa) proteins that are important for the organization of tissues during development and regulate cell motility and localization both during development and in the adult. In the adult, this function is predominately related to the trafficking of leukocytes, although more recently the impact of these molecules on other cell types has become apparent. Chemokines mediate their effects by binding seven transmembrane, G-protein coupled, receptors. In addition to their primary role in regulating cell motility, they can also influence cell survival and proliferation. Antagonists for a number of chemokine receptor have been developed, raising the possibility of interfering with chemokine function as a therapeutic tool. This review focuses on the emerging roles for chemokines in normal physiology and disease.
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    CXC chemokines and their receptors, A case for a significant biological role in cutaneous wound healing
    (Murcia : F. Hernández, 2008) Zaja-Milatovic, Snjezana; Richmond, Ann
    Wound healing requires a complex series of reactions and interactions among cells and their mediators, resulting in an overlapping series of events including coagulation, inflammation, epithelialization, formation of granulation tissue, matrix and scar formation. Cytokines and chemokines promote inflammation, angiogenesis, facilitate the passage of leukocytes from circulation into the tissue, and contribute to the regulation of epithelialization. They integrate inflammatory events and reparative processes that are important for modulating wound healing. Thus both cytokines and chemokines are important targets for therapeutic intervention. The chemokine-mediated regulation of angiogenesis is highly sophisticated, fine tuned, and involves proangiogenic chemokines, including CXCL1-3, 5-8 and their receptors, CXCR1 and CXCR2. CXCL1 and CXCR2 are expressed in normal human epidermis and are further induced during the wound healing process of human burn wounds, especially during the inflammatory, epithelialization and angiogenic processes. Human skin explant studies also show CXCR2 is expressed in wounded keratinocytes and Th/1/Th2 cytokine modulation of CXCR2 expression correlates with proliferation of epidermal keratinocytes. Murine excision wound healing, chemical burn wounds and skin organ culture systems are valuable models for examining the role of inflammatory cytokines and chemokines in wound healing.
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    Detection of CX3CR1 single nucleotide polymorphism and expression on archived eyes with age-related macular degeneration
    (Murcia : F. Hernández, 2005) Chan, C.C.; Tuo, J.; Bojanowski, C.M.; Csaky, K.G.; Green, W.R.
    There is a significant genetic component in age-related macular degeneration (AMD). CX3CR1, which encodes the fractalkine (chemokine, CX3CL1) receptor, has two single nucleotide polymorphisms (SNPs): V249I and T280M. These SNPs are correlated with other aged-related diseases such as atherosclerosis. We have reported an association of CX3CR1 SNP and AMD. In this study we examined CX3CR1 SNP frequencies and protein expression on archived sections of AMD and normal eyes. We microdissected nonretinal, peripheral retinal and macular cells from archived slides of eyes of AMD patients and normal subjects. CX3CR1 SNP typing was conducted by PCR and restriction fragment length polymorphism analysis. CX3CR1 transcripts from retinal cells were also measured using RT-PCR. CX3CR1 protein expression was evaluated using avidin-biotin complex immunohistochemistry. We successfully extracted DNA from 32/40 AMD cases and 2/2 normal eyes. Among the 32 AMD cases, 18 had neovascular AMD and 14 had non-neovascular AMD. The M280 allele was detected in 19/64 (32 cases x2) with a frequency of 29.7%, which was significantly higher as compared to the frequency in the normal population (11.2%). We detected CX3CR1 expression in the various retinal cells. CX3CR1 transcript and protein levels were diminished in the macular lesions. This study successfully analyzed CX3CR1 SNP and transcript expression in microdissected cells from archived paraffin fixed slides. Our data suggest that the M280 allele, a SNP resulting in aberrant CX3CR1 and CX3CL1 interaction, as well as lowered expression of macular CX3CR1, may contribute to the development of AMD.
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    Emerging role of tissue lectins as microenvironmental effectors in tumors and wounds
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Smetana, Karel Jr.; Szabo, Pavol; Gál, Peter; André, Sabine; Gabius, Hans-Joachim; Kodet, Ondřej; Dvořánková, Barbora
    Detailed comparative analysis of at first sight not related process cascades is a means toward this aim: to trace common effector mechanisms and hereby eventually inspire innovative routes for therapeutic management. Following this concept, promotion of tumor progression by stroma, especially cancerassociated fibroblasts and smooth muscle actin-positive myofibroblasts, and beneficial activity of respective cells in wound healing have helped to delineate the involvement of endogenous lectins of the family of galectins. In addition to initiating conversion of fibroblasts to myofibroblasts, galectin-1 instructs the cells to produce a structurally complex extracellular matrix. This bioscaffold is useful for keratinocyte culture, also apparently operative in ameliorating wound healing. These functional aspects encourage to study in detail how lectin-(glycan) counterreceptor display is orchestrated. Such insights are assumed to have potential to contribute to rationally manipulate stem/precursor cells as resource in regenerative medicine.
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    Inflammatory cytokine and chemokine expression in sympathetic ophthalmia: a pilot study
    (F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Furusato, Emiko; Shen, DeFen; Cao, Xiaoguang; Furusato, Bungo; Nussenblat, Robert B.; Rushing, Elisabeth J.; Chan, Chi-Chao
    Sympathetic ophthalmia is a bilateral uveitis that develops after penetrating injury to one eye. This study aimed to identify the inflammatory cellular sub-phenotypes and expression of pertinent inflammatory cytokines/chemokines in sympathetic ophthalmia (SO). Dalen-Fuchs nodules (DFN), granulomas, and non-granulomatous foci of inflammation were micro-dissected from 15 cases. RNA was extracted, and quantitative PCR was performed to measure IL-17, IL-18, IL-23, IFN-γ, CCL19, CXCL11, CCL17, and CCL22 transcripts. Immunohistochemical methods were used to characterize CD3, CD4, CD8, CD20, CD68, and CD163 expression. Non-granulomatous lymphocytes were predominantly CD3-positive and expressed more IFN-γ than cells within granulomas, consistent with Th1 cells. In contrast, granulomas and DFN contained mainly CD68+, CD163+/- and expressed more IL-17, IL-18, IL-23, CCL19, and CXCL11 than non-granulomatous cells. Our data indicate for the first time that M1 macrophages are the predominant inflammatory cells within granulomas and DFN of SO. We further observed high levels of IL-17 within granulomas and the presence of Th1 and M1 cells.
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    lntegrin activation by chemokines. Relevance to inflammatory adhesion cascade during T cell migration
    (Murcia : F. Hernández, 2000) Tanaka, Y.
    The adhesive function of integrins is regulated through cytoplasmic signaling induced by several stimuli, whose process is designated "inside-out signaling". A large number of leukocytes are rapidly recruited to the sites of inflammation where they form an essential component of the response to infection, injury, autoimmune disorders, allergy, tumor invasion, atherosclerosis and so on. The recruitment of leukocytes into tissue is regulated by a sequence of interactions between the circulating leukocytes and the endothelial cells. Leukocyte integrins play a pivotal role in leukocyte adhesion to endothelial cells. During the process, the activation of integrins by various chemoattractants, especially chemokines, is essential for integrin-mediated adhesion in which a signal transduced to the leukocyte converts the functionally inactive integrin to an active adhesive configuration. We have proposed that H-Rassensitive activation of phosphoinositide 3 (PI 3)-kinase and subsequent profilin-mediated actin polymerization, can be involved in chemokine-induced integrindependent adhesion of T cells. The present review documents the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemoattractants including chemokines during inflammatory processes. In contrast, various adhesion molecules are known to transduce extracellular information into cytoplasm, which leads to T cell activation and cytokine production from the cells, designated "outside-in signaling". Such a bi-directional "cross-talking" among adhesion molecules and cytokines is most relevant to inflammatory processes by augmenting immune cell migration from circulation into inflamed tissue such as rheumatoid arthritis, tumor invasion, Behget's disease and atherosclerosis.
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    Microanatomy of lymphocyte-endothelial interactions at the high endothelial venules of lymph nodes
    (Murcia: F. Hernández, 2010) Tohya, Kazuo; Umemoto, Eiji; Miyasaka, Masayuki
    Lymphocyte trafficking into lymph nodes and Peyer’s patches is mediated primarily by specifically differentiated venules, called high endothelial venules (HEVs), located in the tissue parenchyma. HEVs have a unique morphology and phenotype, which enables them to interact with circulating lymphocytes efficiently. That is, the HEV endothelial cells have a tall and plump appearance, and constitutively express multiple adhesion molecules and chemokines on their surface. These molecules can interact with cognate receptors on circulating lymphocytes, thereby mediating the stepwise and sequential lymphocyte adhesion and transendothelial migration (TEM) at the HEV endothelial luminal surface. This review summarizes the fine morphological aspects of the unique HEV endothelial cells, with special reference to the spatial distribution of the adhesion molecules and chemokines that regulate lymphocyte migration.
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    Regulated expression of MCP-I by osteoblastic cells in vitro and in vivo
    (Murcia : F. Hernández, 1999) Graves, D.T.; Jiang, Y.; Valente, A.J.
    Inflammation is characterized by the recruitment of leukocytes from the vasculature. Recent studies have implicated chemokines as an important class of mediators that function principally to stimulate leukocyte recruitment, and in some cases, leukocyte activity. There are four defined chemokine subfamilies based on their primary structure, CXC, CC, C and CX3C. Members of the CC chemokine subfamily, such as monocyte chemoattractant protein 1 (MCP-l), are chemotactic for monocytes and other leukocyte subsets. The studies described below focus on the expression of MCP-1 in vitro and in vivo in an osseous environment. These studies indicate that MCP-1 is typically not expressed in normal bone or by normal osteoblasts in vitro. Upon stimulation by inflammatory mediators, MCP-1 is up-regulated. This expression is temporally and spatially associated with the recruitment of monocytes in both osseous inflammation and during developmentally regulated bone remodelling. Furthermore, exogenous MCP-1 applied to inflamed bone enhances the recruitment of monocytes. Because monocytes produce factors that influence osseous metabolism, including but not limited to prostglandins, platelet-derived growth factor, interleukin-l or tumor necrosis factor, chemokines that initiate their recruitment are likely to be highly important.
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    The role of the CXCR4/CXCL12 axis and its clinical implications in gastric cancer
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Lee, Hyo Jin; Jo, Deog Yeon
    Gastric cancer is the second leading cause of cancer deaths worldwide. Despite the extensive body of research on gastric cancer, the prognosis of patients with advanced gastric cancer remains poor, and therapy for advanced gastric cancer relies largely on cytotoxic chemotherapy. Therefore, identifying the distinct molecular pathways underlying disease progression and treatment resistance may lead to novel therapeutic approaches, as well as improve the quality of life and survival of patients. The chemokine CXCL12 and its receptor CXCR4 are now known to play an important role in cancer development and progression. Here, we review the expression and function of CXCR4 and CXCL12, as well as their clinical relevance in gastric cancer. We also cover the current molecular mechanism, specifically the cell-signaling pathway, by which gastric cancer progresses through the CXCR4/CXCL12 axis, and discuss the potential of that axis as a therapeutic target in the treatment of gastric cancer