The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Sun Ying - One of the best experts on this subject based on the ideXlab platform.
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expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease
Journal of Immunology, 2008Co-Authors: Sun Ying, Brian J Oconnor, Jonathan Ratoff, Qiu Meng, David J Cousins, Guizhen Zhang, Cailong Fang, Zhongli Gao, Betty Shamji, Matthew J EdwardsAbstract:Asthma and chronic obstructive pulmonary disease (COPD) are associated with Th2 and Th1 differentiated T cells. The cytokine thymic stromal lymphopoietin (TSLP) promotes differentiation of Th2 T cells and secretion of chemokines which preferentially attract them. We hypothesized that there is distinct airways expression of TSLP and chemokines which preferentially attract Th1- and Th2-type T cells, and influx of T cells bearing their receptors in asthma and COPD. In situ hybridization, immunohistochemistry, and ELISA were used to examine the expression and cellular provenance of TSLP, Th2-attracting (TARC/CCL17, MDC/CCL22, I-309/CCL1), and Th1-attracting (IP-10/CXCL10, I-TAC/CXCL11) chemokines in the bronchial mucosa and bronchoalveolar lavage fluid of subjects with moderate/severe asthma, COPD, and controls. Cells expressing mRNA encoding TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in severe asthma and COPD as compared with non-smoker controls (p < 0.02). This pattern was reflected in bronchoalveolar lavage fluid protein concentrations. Expression of the same chemokines was also increased in ex- and current smokers. The cellular sources of TSLP and chemokines were strikingly similar in severe asthma and COPD. The numbers of total bronchial mucosal T cells expressing the chemokine receptors CCR4, CCR8, and CXCR3 did not significantly differ in asthma, COPD, and controls. Both asthma and COPD are associated with elevated bronchial mucosal expression of TSLP and the same Th1- and Th2-attracting chemokines. Increased expression of these chemokines is not, however, associated with selective accumulation of T cells bearing their receptors.
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thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of th2 attracting chemokines and disease severity
Journal of Immunology, 2005Co-Authors: Sun Ying, Brian J Oconnor, Jonathan Ratoff, Qiu Meng, K Mallett, David J Cousins, Douglas S Robinson, Guizhen Zhang, Jisheng Zhao, T H LeeAbstract:Thymic stromal lymphopoietin (TSLP) is said to increase expression of chemokines attracting Th2 T cells. We hypothesized that asthma is characterized by elevated bronchial mucosal expression of TSLP and Th2-attracting, but not Th1-attracting, chemokines as compared with controls, with selective accumulation of cells bearing receptors for these chemokines. We used in situ hybridization and immunohistochemistry to examine the expression and cellular provenance of TSLP, Th2-attracting (thymus and activation-regulated chemokine (TARC)/CCL17, macrophage-derived chemokine (MDC)/CCL22, I-309/CCL1) and Th1-attracting (IFN-gamma-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T cell alpha-chemoattractant (I-TAC)/CXCL11) chemokines and expression of their receptors CCR4, CCR8, and CXCR3 in bronchial biopsies from 20 asthmatics and 15 normal controls. The numbers of cells within the bronchial epithelium and submucosa expressing mRNA for TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in asthmatics as compared with controls (p CCL17 expression correlated with airway obstruction. Although the total numbers of cells expressing CCR4, CCR8, and CXCR3 did not significantly differ in the asthmatics and controls, there was evidence of selective infiltration of CD4(+)/CCR4(+) T cells in the asthmatic biopsies which correlated with TARC and MDC expression and airway obstruction. Epithelial cells, endothelial cells, neutrophils, macrophages, and mast cells were significant sources of TSLP and chemokines. Our data implicate TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10 in asthma pathogenesis. These may act partly through selective development and retention, or recruitment of Th2 cells bearing their receptors.
James E. Pease - One of the best experts on this subject based on the ideXlab platform.
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CCL17 thymus and activation regulated chemokine induces calcitonin gene related peptide in human airway epithelial cells through ccr4
The Journal of Allergy and Clinical Immunology, 2013Co-Authors: Kandace Bonner, James E. Pease, C J Corrigan, Peter Clark, Barry A KayAbstract:Background Calcitonin gene–related peptide (CGRP) is a potent arterial and venous vasodilator. Increased airway epithelial cell expression of CGRP, together with increased CCL17 expression, was previously observed in a model of provoked asthma in atopic human subjects. Objective We sought to determine whether CCL17 induces CCR4-dependent CGRP synthesis and secretion by human airway epithelial cells. Methods Human airway epithelial cell lines (BEAS-2B and A549) and human primary airway cells were cultured with CCL17 or various other cytokines, and CGRP expression was measured by using RT-PCR, quantitative immunofluorescence, and enzyme immunoassay. CCR4 expression was determined in cultured cells by using flow cytometry and in bronchial biopsy specimens by using immunohistochemistry. Results CCL17 induced a several thousand–fold increase in CGRP mRNA expression and released peptide product from BEAS-2B and A549 cells in a time- and concentration-dependent fashion. Concentration-dependent CCL17-induced release of CGRP by primary human airway epithelial cells was also observed. Under comparable conditions, CCL17 induced greater CGRP release from BEAS-2B cells than either IL-13, a cytokine mixture (TNF-α, GM-CSF, and IL-1), or CCL22. CCR4 was expressed by BEAS-2B and A549 cells and internalized after ligation with CCL17. CCL17-induced CGRP release was inhibited by a specific anti-CCR4 blocking antibody. Bronchial biopsy specimens obtained from healthy volunteers and asthmatic patients before and after provoked asthma all exhibited CCR4 staining of equivalent intensity, indicating that the receptor is constitutively expressed. Conclusions CCL17-induced, CCR4-dependent release of CGRP by human airway epithelial cells represents a novel inflammatory pathway and a possible target in patients with asthma and allergic disease.
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structure function relationships of ccr8 agonists and antagonists amino terminal extension of ccl1 by a single amino acid generates a partial agonist
Journal of Biological Chemistry, 2006Co-Authors: James M Fox, Pilar Najarro, Geoffrey L Smith, Sofie Struyf, Paul Proost, James E. PeaseAbstract:We describe here the interactions of CCR8 with its ligands using both CCR8 transfectants and a T-cell line expressing the receptor endogenously. Of the CCR8 agonists reported previously, only CCL1 and vMIP-I exhibited potency in assays of intracellular calcium flux, chemotaxis, and receptor internalization, this latter mechanism being dependent upon the expression of beta-arrestins 1 and 2 but independent of Galpha(i) signaling. NH(2)-terminal extension of the mature CCL1 sequence by a serine residue (Ser-CCL1) resulted in a partial agonist with a reduced affinity for CCR8, suggesting that the NH(2) terminus of the ligand plays a role in ligand binding to an intrahelical site. Attempts to identify key residues within this site revealed that the conserved glutamic acid residue in transmembrane helix 7, Glu-286, is crucial for trafficking of the receptor to the cell surface, while Asp-97 of transmembrane helix 2 is dispensable. CCL7 was found to inhibit both Ser-CCL1 and vMIP-I responses but not those of CCL1 itself. Similarly, vMIP-I responses were more than 2 orders of magnitude more sensitive to the specific CCR8 antagonist MC148 than those induced by CCL1, which is difficult to reconcile with the reported affinities for the receptor. Collectively, these data suggest that the CCR8 ligands are allotropic, binding to distinct sites within CCR8 and that the human immune system may have evolved to use CCL7 as a selective antagonist of viral chemokine activity at CCR8 but not those of the host ligand.
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The carboxyl terminus of the chemokine receptor CCR3 contains distinct domains which regulate chemotactic signaling and receptor down‐regulation in a ligand‐dependent manner
European journal of immunology, 2005Co-Authors: Ian Sabroe, Victoria E L Stubbs, Annelies Jorritsma, Georgina Xanthou, Louise A. Jopling, Paul D. Ponath, Timothy J. Williams, Philip M. Murphy, James E. PeaseAbstract:The chemokine receptor CCR3 regulates the chemotaxis of leukocytes implicated in allergic disease, such as eosinophils. Incubation of eosinophils with CCL11, CCL13 or CCL5 resulted in a rapid decrease of cell-surface CCR3 which was replicated using CCR3 transfectants. Progressive truncation of the CCR3 C terminus by 15 amino acids produced three constructs, Δ340, Δ325 and Δ310. Δ340 and Δ325 were able to bind CCL11 with affinities similar to wild-type CCR3. Δ340 transfectants exhibited enhanced migration and reduced receptor down-regulation in response to CCL11 and CCL13. Δ325 transfectants displayed chemotactic responses to CCL11 and CCL13 similar to wild-type CCR3, and had impaired down-regulation when stimulated with CCL13 but not CCL11. In contrast, neither the Δ325 nor Δ340 truncation affected chemotaxis or receptor down-regulation induced by CCL5. Δ310 transfectants bound CCL11 poorly and were biologically inactive. Inhibitors of p38 mitogen-activated protein kinase and PI3-kinase antagonized eosinophil shape change responses and chemotaxis of transfectants to CCL11 and CCL13. In contrast, shape change but not chemotaxis was sensitive to inhibition of the extracellular signal-regulated kinase kinase pathway suggesting differential regulation of the two responses. Thus, the CCR3 C terminus contains distinct domains responsible for the regulation of receptor desensitization and for coupling to chemotactic responses.
Qiu Meng - One of the best experts on this subject based on the ideXlab platform.
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expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease
Journal of Immunology, 2008Co-Authors: Sun Ying, Brian J Oconnor, Jonathan Ratoff, Qiu Meng, David J Cousins, Guizhen Zhang, Cailong Fang, Zhongli Gao, Betty Shamji, Matthew J EdwardsAbstract:Asthma and chronic obstructive pulmonary disease (COPD) are associated with Th2 and Th1 differentiated T cells. The cytokine thymic stromal lymphopoietin (TSLP) promotes differentiation of Th2 T cells and secretion of chemokines which preferentially attract them. We hypothesized that there is distinct airways expression of TSLP and chemokines which preferentially attract Th1- and Th2-type T cells, and influx of T cells bearing their receptors in asthma and COPD. In situ hybridization, immunohistochemistry, and ELISA were used to examine the expression and cellular provenance of TSLP, Th2-attracting (TARC/CCL17, MDC/CCL22, I-309/CCL1), and Th1-attracting (IP-10/CXCL10, I-TAC/CXCL11) chemokines in the bronchial mucosa and bronchoalveolar lavage fluid of subjects with moderate/severe asthma, COPD, and controls. Cells expressing mRNA encoding TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in severe asthma and COPD as compared with non-smoker controls (p < 0.02). This pattern was reflected in bronchoalveolar lavage fluid protein concentrations. Expression of the same chemokines was also increased in ex- and current smokers. The cellular sources of TSLP and chemokines were strikingly similar in severe asthma and COPD. The numbers of total bronchial mucosal T cells expressing the chemokine receptors CCR4, CCR8, and CXCR3 did not significantly differ in asthma, COPD, and controls. Both asthma and COPD are associated with elevated bronchial mucosal expression of TSLP and the same Th1- and Th2-attracting chemokines. Increased expression of these chemokines is not, however, associated with selective accumulation of T cells bearing their receptors.
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thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of th2 attracting chemokines and disease severity
Journal of Immunology, 2005Co-Authors: Sun Ying, Brian J Oconnor, Jonathan Ratoff, Qiu Meng, K Mallett, David J Cousins, Douglas S Robinson, Guizhen Zhang, Jisheng Zhao, T H LeeAbstract:Thymic stromal lymphopoietin (TSLP) is said to increase expression of chemokines attracting Th2 T cells. We hypothesized that asthma is characterized by elevated bronchial mucosal expression of TSLP and Th2-attracting, but not Th1-attracting, chemokines as compared with controls, with selective accumulation of cells bearing receptors for these chemokines. We used in situ hybridization and immunohistochemistry to examine the expression and cellular provenance of TSLP, Th2-attracting (thymus and activation-regulated chemokine (TARC)/CCL17, macrophage-derived chemokine (MDC)/CCL22, I-309/CCL1) and Th1-attracting (IFN-gamma-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T cell alpha-chemoattractant (I-TAC)/CXCL11) chemokines and expression of their receptors CCR4, CCR8, and CXCR3 in bronchial biopsies from 20 asthmatics and 15 normal controls. The numbers of cells within the bronchial epithelium and submucosa expressing mRNA for TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in asthmatics as compared with controls (p CCL17 expression correlated with airway obstruction. Although the total numbers of cells expressing CCR4, CCR8, and CXCR3 did not significantly differ in the asthmatics and controls, there was evidence of selective infiltration of CD4(+)/CCR4(+) T cells in the asthmatic biopsies which correlated with TARC and MDC expression and airway obstruction. Epithelial cells, endothelial cells, neutrophils, macrophages, and mast cells were significant sources of TSLP and chemokines. Our data implicate TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10 in asthma pathogenesis. These may act partly through selective development and retention, or recruitment of Th2 cells bearing their receptors.
David J Cousins - One of the best experts on this subject based on the ideXlab platform.
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expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease
Journal of Immunology, 2008Co-Authors: Sun Ying, Brian J Oconnor, Jonathan Ratoff, Qiu Meng, David J Cousins, Guizhen Zhang, Cailong Fang, Zhongli Gao, Betty Shamji, Matthew J EdwardsAbstract:Asthma and chronic obstructive pulmonary disease (COPD) are associated with Th2 and Th1 differentiated T cells. The cytokine thymic stromal lymphopoietin (TSLP) promotes differentiation of Th2 T cells and secretion of chemokines which preferentially attract them. We hypothesized that there is distinct airways expression of TSLP and chemokines which preferentially attract Th1- and Th2-type T cells, and influx of T cells bearing their receptors in asthma and COPD. In situ hybridization, immunohistochemistry, and ELISA were used to examine the expression and cellular provenance of TSLP, Th2-attracting (TARC/CCL17, MDC/CCL22, I-309/CCL1), and Th1-attracting (IP-10/CXCL10, I-TAC/CXCL11) chemokines in the bronchial mucosa and bronchoalveolar lavage fluid of subjects with moderate/severe asthma, COPD, and controls. Cells expressing mRNA encoding TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in severe asthma and COPD as compared with non-smoker controls (p < 0.02). This pattern was reflected in bronchoalveolar lavage fluid protein concentrations. Expression of the same chemokines was also increased in ex- and current smokers. The cellular sources of TSLP and chemokines were strikingly similar in severe asthma and COPD. The numbers of total bronchial mucosal T cells expressing the chemokine receptors CCR4, CCR8, and CXCR3 did not significantly differ in asthma, COPD, and controls. Both asthma and COPD are associated with elevated bronchial mucosal expression of TSLP and the same Th1- and Th2-attracting chemokines. Increased expression of these chemokines is not, however, associated with selective accumulation of T cells bearing their receptors.
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thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of th2 attracting chemokines and disease severity
Journal of Immunology, 2005Co-Authors: Sun Ying, Brian J Oconnor, Jonathan Ratoff, Qiu Meng, K Mallett, David J Cousins, Douglas S Robinson, Guizhen Zhang, Jisheng Zhao, T H LeeAbstract:Thymic stromal lymphopoietin (TSLP) is said to increase expression of chemokines attracting Th2 T cells. We hypothesized that asthma is characterized by elevated bronchial mucosal expression of TSLP and Th2-attracting, but not Th1-attracting, chemokines as compared with controls, with selective accumulation of cells bearing receptors for these chemokines. We used in situ hybridization and immunohistochemistry to examine the expression and cellular provenance of TSLP, Th2-attracting (thymus and activation-regulated chemokine (TARC)/CCL17, macrophage-derived chemokine (MDC)/CCL22, I-309/CCL1) and Th1-attracting (IFN-gamma-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T cell alpha-chemoattractant (I-TAC)/CXCL11) chemokines and expression of their receptors CCR4, CCR8, and CXCR3 in bronchial biopsies from 20 asthmatics and 15 normal controls. The numbers of cells within the bronchial epithelium and submucosa expressing mRNA for TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in asthmatics as compared with controls (p CCL17 expression correlated with airway obstruction. Although the total numbers of cells expressing CCR4, CCR8, and CXCR3 did not significantly differ in the asthmatics and controls, there was evidence of selective infiltration of CD4(+)/CCR4(+) T cells in the asthmatic biopsies which correlated with TARC and MDC expression and airway obstruction. Epithelial cells, endothelial cells, neutrophils, macrophages, and mast cells were significant sources of TSLP and chemokines. Our data implicate TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10 in asthma pathogenesis. These may act partly through selective development and retention, or recruitment of Th2 cells bearing their receptors.
Jonathan Ratoff - One of the best experts on this subject based on the ideXlab platform.
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expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease
Journal of Immunology, 2008Co-Authors: Sun Ying, Brian J Oconnor, Jonathan Ratoff, Qiu Meng, David J Cousins, Guizhen Zhang, Cailong Fang, Zhongli Gao, Betty Shamji, Matthew J EdwardsAbstract:Asthma and chronic obstructive pulmonary disease (COPD) are associated with Th2 and Th1 differentiated T cells. The cytokine thymic stromal lymphopoietin (TSLP) promotes differentiation of Th2 T cells and secretion of chemokines which preferentially attract them. We hypothesized that there is distinct airways expression of TSLP and chemokines which preferentially attract Th1- and Th2-type T cells, and influx of T cells bearing their receptors in asthma and COPD. In situ hybridization, immunohistochemistry, and ELISA were used to examine the expression and cellular provenance of TSLP, Th2-attracting (TARC/CCL17, MDC/CCL22, I-309/CCL1), and Th1-attracting (IP-10/CXCL10, I-TAC/CXCL11) chemokines in the bronchial mucosa and bronchoalveolar lavage fluid of subjects with moderate/severe asthma, COPD, and controls. Cells expressing mRNA encoding TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in severe asthma and COPD as compared with non-smoker controls (p < 0.02). This pattern was reflected in bronchoalveolar lavage fluid protein concentrations. Expression of the same chemokines was also increased in ex- and current smokers. The cellular sources of TSLP and chemokines were strikingly similar in severe asthma and COPD. The numbers of total bronchial mucosal T cells expressing the chemokine receptors CCR4, CCR8, and CXCR3 did not significantly differ in asthma, COPD, and controls. Both asthma and COPD are associated with elevated bronchial mucosal expression of TSLP and the same Th1- and Th2-attracting chemokines. Increased expression of these chemokines is not, however, associated with selective accumulation of T cells bearing their receptors.
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thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of th2 attracting chemokines and disease severity
Journal of Immunology, 2005Co-Authors: Sun Ying, Brian J Oconnor, Jonathan Ratoff, Qiu Meng, K Mallett, David J Cousins, Douglas S Robinson, Guizhen Zhang, Jisheng Zhao, T H LeeAbstract:Thymic stromal lymphopoietin (TSLP) is said to increase expression of chemokines attracting Th2 T cells. We hypothesized that asthma is characterized by elevated bronchial mucosal expression of TSLP and Th2-attracting, but not Th1-attracting, chemokines as compared with controls, with selective accumulation of cells bearing receptors for these chemokines. We used in situ hybridization and immunohistochemistry to examine the expression and cellular provenance of TSLP, Th2-attracting (thymus and activation-regulated chemokine (TARC)/CCL17, macrophage-derived chemokine (MDC)/CCL22, I-309/CCL1) and Th1-attracting (IFN-gamma-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T cell alpha-chemoattractant (I-TAC)/CXCL11) chemokines and expression of their receptors CCR4, CCR8, and CXCR3 in bronchial biopsies from 20 asthmatics and 15 normal controls. The numbers of cells within the bronchial epithelium and submucosa expressing mRNA for TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in asthmatics as compared with controls (p CCL17 expression correlated with airway obstruction. Although the total numbers of cells expressing CCR4, CCR8, and CXCR3 did not significantly differ in the asthmatics and controls, there was evidence of selective infiltration of CD4(+)/CCR4(+) T cells in the asthmatic biopsies which correlated with TARC and MDC expression and airway obstruction. Epithelial cells, endothelial cells, neutrophils, macrophages, and mast cells were significant sources of TSLP and chemokines. Our data implicate TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10 in asthma pathogenesis. These may act partly through selective development and retention, or recruitment of Th2 cells bearing their receptors.