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Andrew D Luster - One of the best experts on this subject based on the ideXlab platform.

  • Eotaxin expression after segmental allergen challenge in subjects with atopic asthma
    American Journal of Respiratory and Critical Care Medicine, 2001
    Co-Authors: Craig M. Lilly, Kathleen J. Haley, Andrew D Luster, Eduardo A Garciazepeda, Hidetoshi Nakamura, Olga I Belostotsky, Elliot Israel
    Abstract:

    Expression of pulmonary Eotaxin protein and mRNA was determined in six subjects with atopic asthma and five nonatopic normal subjects. Levels of Eotaxin expression and eosinophil mobilization were compared before and after segmental allergen challenge in subjects with atopic asthma. In the absence of allergen challenge, we found significantly higher levels of Eotaxin in the bronchoalveolar lavage (BAL) fluid of subjects with asthma than in that of normal subjects (25 ± 3 versus 15 ± 2 pg/ml, p < 0.05). BAL Eotaxin levels increased after segmental allergen challenge in all six subjects with atopic asthma tested, with a mean increase from 22 ± 4 to 53 ± 10 pg/ml (p = 0.013). Segmental allergen challenge was associated with a significant increase in the percentage of BAL macrophages and eosinophils that were immunopositive for Eotaxin. Eotaxin mRNA was detectable by northern analysis in BAL cells exclusively from allergen-challenged segments. Allergen- induced increases in Eotaxin levels were strongly associ...

  • Eotaxin and impaired lung function in asthma
    American Journal of Respiratory and Critical Care Medicine, 1999
    Co-Authors: Hidetoshi Nakamura, Andrew D Luster, Jeffrey M Drazen, Elliot Israel, Scott T Weiss, Craig M. Lilly
    Abstract:

    We performed an association study of plasma Eotaxin levels, eosinophil counts, total IgE levels, asthma diagnosis, and lung function in an ethnically diverse and geographically dispersed population. We studied 515 asthmatic and 519 normal subjects, none of whom was taking inhaled or oral corticosteroids. Logistic regression analysis demonstrated a direct relationship between asthma diagnosis and Eotaxin levels (p < 0.0001). The odds of an asthma diagnosis increased with Eotaxin quartile, with the highest quartile having an odds ratio of 5.4 (95% CI 3.2 to 9.2, p < 0.001) compared with the lowest Eotaxin quartile. Eotaxin levels were inversely related to lung function (p < 0.001), with the mean percent predicted FEV1 in the highest Eotaxin quartile being 13.5 percentage points (SEM 2.1, p < 0.001) less than that in the lowest quartile. Plasma Eotaxin levels were associated with asthma and inversely related to lung function independent of age, race, sex, or smoking status. When combined with eosinophil coun...

  • constitutive and cytokine stimulated expression of Eotaxin by human airway smooth muscle cells
    American Journal of Respiratory and Critical Care Medicine, 1999
    Co-Authors: Omar Ghaffar, Andrew D Luster, Qutayba Hamid, Paolo M Renzi, Zoulfia Allakhverdi, Sophie Molet, James C Hogg, Stephanie A Shore, Bouchaib Lamkhioued
    Abstract:

    Airway eosinophilia is a prominent feature of asthma that is believed to be mediated in part through the expression of specific chemokines such as Eotaxin, a potent eosinophil chemoattractant that is highly expressed by epithelial cells and inflammatory cells in asthmatic airways. Airway smooth muscle (ASM) has been identified as a potential source of cytokines and chemokines. The aim of the present study was to examine the capacity of human ASM to express Eotaxin. We demonstrate that airway myocytes constitutively express Eotaxin mRNA as detected by RT-PCR. Treatment of ASM for 24 h with different concentrations of TNF- α and IL-1 β alone or in combination enhanced the accumulation of Eotaxin transcripts. Maximal mRNA expression of Eotaxin was shown at 12 and 24 h following IL-1 β and TNF- α stimulation, respectively. The presence of immunoreactive Eotaxin was demonstrated by immunocytochemistry, and constitutive and cytokine-stimulated release of Eotaxin was confirmed in ASM culture supernatants by ELIS...

  • Eotaxin is required for the baseline level of tissue eosinophils
    Proceedings of the National Academy of Sciences of the United States of America, 1998
    Co-Authors: Angela N Matthews, Daniel S. Friend, Nives Zimmermann, Andrew D Luster, Eric Pearlman, Mindy N Sarafi, Susan E Wert, Marc E Rothenberg
    Abstract:

    Eotaxin is an eosinophil-selective chemokine that is constitutively expressed in a variety of organs such as the intestine. Previous studies have demonstrated that the recruitment of eosinophils during inflammation is partially dependent on Eotaxin, but the function of constitutive Eotaxin during homeostasis has not been examined. To elucidate the biological role of this molecule, we now examine tissue levels of eosinophils in healthy states in wild-type and Eotaxin-deficient mice. The lamina propria of the jejunum of wild-type mice is demonstrated to express Eotaxin mRNA, but not mRNA for the related monocyte chemoattractant proteins. Wild-type mice contained readily detectable eosinophils in the lamina propria of the jejunum. In contrast, mice genetically deficient in Eotaxin had a large selective reduction in the number of eosinophils residing in the jejunum. The reduction of tissue eosinophils was not limited to the jejunum, because a loss of thymic eosinophils was also observed in Eotaxin-deficient mice. These studies demonstrate that Eotaxin is a fundamental regulator of the physiological trafficking of eosinophils during healthy states. Because a variety of chemokines are constitutively expressed, their involvement in the baseline trafficking of leukocytes into nonhematopoietic tissue should now be considered.

  • Eotaxin mrna and protein expression in chronic sinusitis and allergen induced nasal responses in seasonal allergic rhinitis
    American Journal of Respiratory Cell and Molecular Biology, 1997
    Co-Authors: E M Minshall, Marc E Rothenberg, Andrew D Luster, Lisa Cameron, F Lavigne, Donald Y M Leung, Daniel L Hamilos, E A Garciazepada, Qutayba Hamid
    Abstract:

    Eotaxin is an eosinophil-specific chemokine associated with the recruitment of eosinophils to the site of allergic inflammation. The aims of this study were to determine the expression of Eotaxin in nasal biopsies from allergic and nonallergic individuals with chronic severe sinusitis, and to examine whether the expression of this chemokine is upregulated following allergen challenge in the nasal mucosa of patients with allergic rhinitis. We also undertook to phenotype of inflammatory cells within the submucosa expressing Eotaxin mRNA. Nasal turbinate tissue from 16 individuals with allergic or nonallergic chronic sinusitis and 10 normal controls were examined for the presence of Eotaxin mRNA and immunoreactivity by in situ hybridization and immunocytochemistry. The numbers of cells expressing Eotaxin mRNA were also determined after either allergen or diluent challenge in atopic subjects with a history of allergic rhinitis. There was a constitutive expression of Eotaxin-immunoreactivity and the presence o...

Marc E Rothenberg - One of the best experts on this subject based on the ideXlab platform.

  • epigenetic regulation of the il 13 induced human Eotaxin 3 gene by creb binding protein mediated histone 3 acetylation
    Journal of Biological Chemistry, 2011
    Co-Authors: Thomas X Lu, Carine Blanchard, Marc E Rothenberg
    Abstract:

    The etiology of a variety of chronic inflammatory disorders has been attributed to the interaction of genetic and environmental factors. Herein, we identified a link between epigenetic regulation and IL-13-driven Eotaxin-3 in the pathogenesis of chronic allergic inflammation. We first demonstrated that the cAMP-responsive element (CRE) site in the Eotaxin-3 promoter affects IL-13-induced Eotaxin-3 promoter activity. Furthermore, the CRE-binding protein-binding protein (CBP), a histone acetyltransferase, induced base-line and IL-13-induced Eotaxin-3 promoter activity. Additionally, IL-13 treatment promoted global histone 3 acetylation as well as the formation of a complex containing CBP and STAT6 and the subsequent acetylation of histone 3 at the Eotaxin-3 promoter. CBP gene silencing decreased IL-13-induced transcription of Eotaxin-3. Conversely, inhibition of histone deacetylation increased IL-13-induced Eotaxin-3 production. Clinical studies demonstrated markedly increased global acetylation of histone 3 in the inflamed tissue of patients with allergic inflammation. Collectively, these results identify an epigenetic mechanism involving CBP and chromatin remodeling in regulating IL-13-induced chemokine transcription.

  • the Eotaxin chemokines and ccr3 are fundamental regulators of allergen induced pulmonary eosinophilia
    Journal of Immunology, 2005
    Co-Authors: Samuel M Pope, Keith F Stringer, Nives Zimmermann, Margaret Karow, Marc E Rothenberg
    Abstract:

    The Eotaxin chemokines have been implicated in allergen-induced eosinophil responses in the lung. However, the individual and combined contribution of each of the individual Eotaxins is not well defined. We aimed to examine the consequences of genetically ablating Eotaxin-1 or Eotaxin-2 alone, Eotaxin-1 and Eotaxin-2 together, and CCR3. Mice carrying targeted deletions of these individual or combined genes were subjected to an OVA-induced experimental asthma model. Analysis of airway (luminal) eosinophilia revealed a dominant role for Eotaxin-2 and a synergistic reduction in Eotaxin-1/2 double-deficient (DKO) and CCR3-deficient mice. Examination of pulmonary tissue eosinophilia revealed a modest role for individually ablated Eotaxin-1 or Eotaxin-2. However, Eotaxin-1/2 DKO mice had a marked decrease in tissue eosinophilia approaching the low levels seen in CCR3-deficient mice. Notably, the organized accumulation of eosinophils in the peribronchial and perivascular regions of allergen-challenged wild-type mice was lost in Eotaxin-1/2 DKO and CCR3-deficient mice. Mechanistic analysis revealed distinct expression of Eotaxin-2 in bronchoalveolar lavage fluid cells consistent with macrophages. Taken together, these results provide definitive evidence for a fundamental role of the Eotaxin/CCR3 pathway in eosinophil recruitment in experimental asthma. These results imply that successful blockade of Ag-induced pulmonary eosinophilia will require antagonism of multiple CCR3 ligands.

  • identification of a cooperative mechanism involving interleukin 13 and Eotaxin 2 in experimental allergic lung inflammation
    Journal of Biological Chemistry, 2005
    Co-Authors: Samuel M Pope, Carine Blanchard, Nives Zimmermann, Patricia C Fulkerson, Hiroko Saito Akei, Nikolaos M Nikolaidis, Jeffery D Molkentin, Marc E Rothenberg
    Abstract:

    Abstract Pulmonary eosinophilia, a hallmark pathologic feature of allergic lung disease, is regulated by interleukin-13 (IL-13) as well as the Eotaxin chemokines, but the specific role of these cytokines and their cooperative interaction are only partially understood. First, we elucidated the essential role of IL-13 in the induction of the Eotaxins by comparing IL-13 gene-targeted mice with wild type control mice by using an ovalbumin-induced model of allergic airway inflammation. Notably, ovalbumin-induced expressions of Eotaxin-1 and Eotaxin-2 mRNA in the lungs were almost completely dependent upon IL-13. Second, in order to address the specific role of Eotaxin-2 in IL-13-induced pulmonary eosinophilia, we generated Eotaxin-2 gene-deficient mice by homologous recombination. Notably, in contrast to observations made in Eotaxin-1-deficient mice, Eotaxin-2-deficient mice had normal base-line eosinophil levels in the hematopoietic tissues and gastrointestinal tract. However, following intratracheal IL-13 administration, Eotaxin-2-deficient mice showed a profound reduction in airway eosinophilia compared with wild type mice. Most interestingly, the level of peribronchial lung tissue eosinophils in IL-13-treated Eotaxin-2-deficient mice was indistinguishable from wild type mice. Furthermore, IL-13 lung transgenic mice genetically engineered to be deficient in Eotaxin-2 had a marked reduction of luminal eosinophils. Mechanistic analysis identified IL13-induced Eotaxin-2 expression by macrophages in a distinct lung compartment (luminal inflammatory cells) compared with Eotaxin-1, which was expressed solely in the tissue. Taken together, these results demonstrate a cooperative mechanism between IL-13 and Eotaxin-2. In particular, IL-13 mediates allergen-induced Eotaxin-2 expression, and Eotaxin-2 mediates IL-13-induced airway eosinophilia.

  • murine Eotaxin 2 a constitutive eosinophil chemokine induced by allergen challenge and il 4 overexpression
    Journal of Immunology, 2000
    Co-Authors: Nives Zimmermann, Samuel M Pope, Simon P Hogan, Anil Mishra, Eric B Brandt, Thomas R Bodette, F D Finkelman, Marc E Rothenberg
    Abstract:

    The generation of tissue eosinophilia is governed in part by chemokines; initial investigation has identified three chemokines in the human genome with eosinophil selectivity, referred to as Eotaxin-1, -2, and -3. Elucidation of the role of these chemokines is dependent in part upon analysis of murine homologues; however, only one murine homologue, Eotaxin-1, has been identified. We now report the characterization of the murine Eotaxin-2 cDNA, gene and protein. The Eotaxin-2 cDNA contains an open reading frame that encodes for a 119-amino acid protein. The mature protein, which is predicted to contain 93 amino acids, is most homologous to human Eotaxin-2 (59.1% identity), but is only 38.9% identical with murine Eotaxin-1. Northern blot analysis reveals three predominant mRNA species and highest constitutive expression in the jejunum and spleen. Additionally, allergen challenge in the lung with Asperigillus fumigatus or OVA revealed marked induction of Eotaxin-2 mRNA. Furthermore, Eotaxin-2 mRNA was strongly induced by both transgenic over-expression of IL-4 in the lung and administration of intranasal IL-4. Analysis of Eotaxin-2 mRNA expression in mice transgenic for IL-4 but genetically deficient in STAT-6 revealed that the IL-4-induced expression was STAT-6 dependent. Recombinant Eotaxin-2 protein induced dose-dependent chemotactic responses on murine eosinophils at concentrations between 1–1000 ng/ml, whereas no activity was displayed on murine macrophages or neutrophils. Functional analysis of recombinant protein variants revealed a critical role for the amino terminus. Thus, murine Eotaxin-2 is a constitutively expressed eosinophil chemokine likely to be involved in homeostatic, allergen-induced, and IL-4-associated immune responses.

  • Eotaxin is required for the baseline level of tissue eosinophils
    Proceedings of the National Academy of Sciences of the United States of America, 1998
    Co-Authors: Angela N Matthews, Daniel S. Friend, Nives Zimmermann, Andrew D Luster, Eric Pearlman, Mindy N Sarafi, Susan E Wert, Marc E Rothenberg
    Abstract:

    Eotaxin is an eosinophil-selective chemokine that is constitutively expressed in a variety of organs such as the intestine. Previous studies have demonstrated that the recruitment of eosinophils during inflammation is partially dependent on Eotaxin, but the function of constitutive Eotaxin during homeostasis has not been examined. To elucidate the biological role of this molecule, we now examine tissue levels of eosinophils in healthy states in wild-type and Eotaxin-deficient mice. The lamina propria of the jejunum of wild-type mice is demonstrated to express Eotaxin mRNA, but not mRNA for the related monocyte chemoattractant proteins. Wild-type mice contained readily detectable eosinophils in the lamina propria of the jejunum. In contrast, mice genetically deficient in Eotaxin had a large selective reduction in the number of eosinophils residing in the jejunum. The reduction of tissue eosinophils was not limited to the jejunum, because a loss of thymic eosinophils was also observed in Eotaxin-deficient mice. These studies demonstrate that Eotaxin is a fundamental regulator of the physiological trafficking of eosinophils during healthy states. Because a variety of chemokines are constitutively expressed, their involvement in the baseline trafficking of leukocytes into nonhematopoietic tissue should now be considered.

T J Williams - One of the best experts on this subject based on the ideXlab platform.

  • Eotaxin ccl11 and Eotaxin 2 ccl24 induce recruitment of eosinophils basophils neutrophils and macrophages as well as features of early and late phase allergic reactions following cutaneous injection in human atopic and nonatopic volunteers
    Journal of Immunology, 2002
    Co-Authors: Andrew Menziesgow, Sun Ying, Ian Sabroe, Victoria E L Stubbs, Dulce Soler, T J Williams
    Abstract:

    Eotaxin and Eotaxin-2, acting through CCR3, are potent eosinophil chemoattractants both in vitro and in animal models. In this study we examined the capacity of Eotaxin and Eotaxin-2 to recruit eosinophils and other inflammatory cells in vivo in human atopic and nonatopic skin. Skin biopsies taken after intradermal injection of Eotaxin and Eotaxin-2 were examined by immunohistochemistry. Allergen- and diluent-challenged sites were used as positive and negative controls. Eotaxin and Eotaxin-2 produced a dose- and time-dependent local eosinophilia of comparable intensity in both atopic and nonatopic individuals. This was associated with an acute wheal and flare response at the site of injection and development of a cutaneous late phase reaction in a proportion of subjects. There was an accompanying decrease in mast cell numbers. Both chemokines also induced the accumulation of basophils and an unexpected early infiltration of neutrophils. Macrophages were prominent at the 24-h point. Although there was surface CCR3 expression on neutrophils in whole blood, we were unable to demonstrate any functional neutrophil responses to Eotaxin in vitro. Thus, intradermal injection of Eotaxin and Eotaxin-2 in humans induced infiltration of eosinophils and other inflammatory cells as well as changes consistent with CC chemokine-induced mast cell degranulation.

  • Eotaxin is specifically cleaved by hookworm metalloproteases preventing its action in vitro and in vivo
    Journal of Immunology, 2000
    Co-Authors: Fiona J Culley, Ian Sabroe, Alan Brown, Dolores M Conroy, D I Pritchard, T J Williams
    Abstract:

    Eotaxin is a potent eosinophil chemoattractant that acts selectively through CCR3, which is expressed on eosinophils, basophils, mast cells, and Th2-type T cells. This arm of the immune system is believed to have evolved to control helminthic parasites. We hypothesized that helminths may employ mechanisms to inhibit eosinophil recruitment, to prolong worm survival in the host. We observed that the excretory/secretory products of the hookworm Necator americanus inhibited eosinophil recruitment in vivo in response to Eotaxin, but not leukotriene B4, a phenomenon that could be prevented by the addition of protease inhibitors. Using Western blotting, N. americanus supernatant was shown to cause rapid proteolysis of Eotaxin, but not IL-8 or Eotaxin-2. N. americanus homogenate was fractionated by gel filtration chromatography, and a FACS-based bioassay measured the ability of each fraction to inhibit the activity of a variety of chemokines. This resulted in two peaks of Eotaxin-degrading activity, corresponding to ∼15 and 50 kDa molecular mass. This activity was specific for Eotaxin, as responses to other agonists tested were unaffected. Proteolysis of Eotaxin was prevented by EDTA and phenanthroline, indicating that metalloprotease activity was involved. Production of enzymes inactivating Eotaxin may be a strategy employed by helminths to prevent recruitment and activation of eosinophils at the site of infection. As such this represents a novel mechanism of regulation of chemokine function in vivo. The existence of CCR3 ligands other than Eotaxin (e.g., Eotaxin-2) may reflect the evolution of host counter measures to parasite defense systems.

  • chemokine induced eosinophil recruitment evidence of a role for endogenous Eotaxin in an in vivo allergy model in mouse skin
    Journal of Clinical Investigation, 1997
    Co-Authors: Mauro M Teixeira, Timothy N C Wells, Nicholas W Lukacs, Amanda E I Proudfoot, Steven L Kunkel, T J Williams, Paul G Hellewell
    Abstract:

    Selective eosinophil recruitment into tissues is a characteris- tic feature of allergic diseases. Chemokines are effective leu- kocyte chemoattractants and may play an important role in mediating eosinophil recruitment in various allergic condi- tions in man. Here, we describe a novel mouse model of eosinophil recruitment in which we have compared the in vivo chemoattractant activity of different C-C chemokines. Furthermore, we describe the use of antibodies to chemo- kines and receptor blockade to address the endogenous mech- anisms involved in eosinophil recruitment in a late-phase allergic reaction in mouse skin. Intradermal injection of mEotaxin and mMIP-1 a , but not mMCP-1, mRANTES, mMCP-5, or mMIP-1 b , induced significant 111 In-eosinophil recruitment in mouse skin. Significant 111 In-eosinophil re- cruitment was also observed in an active cutaneous anaphy- lactic reaction. Pretreatment of skin sites with antiEotaxin antiserum, but not an antiMIP-1 a antibody, suppressed 111 In-eosinophil recruitment in this delayed-onset allergic reaction. Similarly, desensitization of the eosinophil Eotaxin receptor CCR3 with mEotaxin, or blockade of the receptor with metRANTES, significantly inhibited 111 In-eosinophil recruitment in the allergic reaction. These results demon- strate an important role for endogenous Eotaxin in mediat- ing the 111 In-eosinophil recruitment in allergic inflamma- tion, and suggest that blockade of the CCR3 receptor is a valid strategy to inhibit eosinophil migration in vivo. ( J. Clin. Invest. 1997. 100:1657-1666.) Key words: chemokines • chemokine receptorseosinophilsallergylate-phase re- sponse

  • the chemokine Eotaxin activates guinea pig eosinophils in vitro and causes their accumulation into the lung in vivo
    Biochemical and Biophysical Research Communications, 1993
    Co-Authors: D A Griffithsjohnson, Peter J Jose, P D Collins, A G Rossi, T J Williams
    Abstract:

    Abstract Eotaxin is a novel C-C chemokine purified from the bronchoalveolar lavage (BAL) fluid of actively sensitised guinea-pigs after aerosol allergen challenge. In this study we show that Eotaxin induced a dose-dependent increase in both intracellular-free calcium concentration ([Ca 2+ ] i ) and aggregation of guinea-pig eosinophils in vitro . Intradermally injected Eotaxin induced the accumulation of [ 111 In]eosinophils in naive guinea-pig skin in vivo , without oedema-inducing activity; the latter emerging in separate BAL fluid HPLC fractions. Aerosol exposure of naive guinea-pigs to Eotaxin in vivo caused a selective increase in eosinophils in BAL fluid. Thus, Eotaxin activates guinea-pig eosinophils in vitro and causes a selective eosinophil accumulation in the lung in vivo . Eotaxin and related molecules are potentially important endogenous signalling substances in allergic reactions in vivo .

Hideshi Torii - One of the best experts on this subject based on the ideXlab platform.

  • significant elevation of serum levels of Eotaxin 3 ccl26 but not of Eotaxin 2 ccl24 in patients with atopic dermatitis serum Eotaxin 3 ccl26 levels reflect the disease activity of atopic dermatitis
    Clinical and Experimental Immunology, 2003
    Co-Authors: Shinji Kagami, Takashi Kakinuma, Hidehisa Saeki, Yuichiro Tsunemi, Hideki Fujita, Koichiro Nakamura, Tomonori Takekoshi, Megumi Kishimoto, Hiroshi Mitsui, Hideshi Torii
    Abstract:

    Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of T cells, eosinophils and macrophages in lesional skin. Recently, Eotaxin-2/CCL24 and Eotaxin-3/CCL26 were identified as CC chemokines that signal exclusively via the CCR3 receptor and have eosinophil-selective chemoattractant activity, as does Eotaxin/CCL11. We previously reported that serum levels of thymus and activation-regulated chemokine (TARC)/CCL17 and macrophage-derived chemokine (MDC)/CCL22 were correlated with the severity of AD. In this report, we investigated the participation of Eotaxin-2/CCL24 and Eotaxin-3/CCL26 in AD, first measuring the serum levels of Eotaxin-2/CCL24 and Eotaxin-3/CCL26 in 30 patients with AD, 20 patients with psoriasis vulgaris and 20 healthy controls. The serum levels of Eotaxin-3/CCL26 (but not Eotaxin-2/CCL24) were significantly higher in patients with AD than in either healthy controls or patients with psoriasis vulgaris; furthermore, the Eotaxin-3/CCL26 levels in patients with moderate and severe AD were significantly higher than Eotaxin-3/CCL26 levels in patients with mild AD. The serum Eotaxin-3/CCL26 levels tended to decrease after treatment, but there was no significant difference between groups. Moreover, the serum Eotaxin-3/CCL26 levels were significantly correlated with the serum TARC/CCL17 and MDC/CCL22 levels, eosinophil numbers in peripheral blood and the scoring AD (SCORAD) index. Our study strongly suggests that serum levels of Eotaxin-3/CCL26, but not of Eotaxin-2/CCL24, have a notable correlation with disease activity of AD and that Eotaxin-3/CCL26, as well as TARC/CCL17 and MDC/CCL22, may be involved in the pathogenesis of AD.

  • Significant elevation of serum levels of Eotaxin‐3/CCL26, but not of Eotaxin‐2/CCL24, in patients with atopic dermatitis: serum Eotaxin‐3/CCL26 levels reflect the disease activity of atopic dermatitis
    Clinical and Experimental Immunology, 2003
    Co-Authors: Shinji Kagami, Takashi Kakinuma, Hidehisa Saeki, Yuichiro Tsunemi, Hideki Fujita, Koichiro Nakamura, Tomonori Takekoshi, Megumi Kishimoto, Hiroshi Mitsui, Hideshi Torii
    Abstract:

    Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of T cells, eosinophils and macrophages in lesional skin. Recently, Eotaxin-2/CCL24 and Eotaxin-3/CCL26 were identified as CC chemokines that signal exclusively via the CCR3 receptor and have eosinophil-selective chemoattractant activity, as does Eotaxin/CCL11. We previously reported that serum levels of thymus and activation-regulated chemokine (TARC)/CCL17 and macrophage-derived chemokine (MDC)/CCL22 were correlated with the severity of AD. In this report, we investigated the participation of Eotaxin-2/CCL24 and Eotaxin-3/CCL26 in AD, first measuring the serum levels of Eotaxin-2/CCL24 and Eotaxin-3/CCL26 in 30 patients with AD, 20 patients with psoriasis vulgaris and 20 healthy controls. The serum levels of Eotaxin-3/CCL26 (but not Eotaxin-2/CCL24) were significantly higher in patients with AD than in either healthy controls or patients with psoriasis vulgaris; furthermore, the Eotaxin-3/CCL26 levels in patients with moderate and severe AD were significantly higher than Eotaxin-3/CCL26 levels in patients with mild AD. The serum Eotaxin-3/CCL26 levels tended to decrease after treatment, but there was no significant difference between groups. Moreover, the serum Eotaxin-3/CCL26 levels were significantly correlated with the serum TARC/CCL17 and MDC/CCL22 levels, eosinophil numbers in peripheral blood and the scoring AD (SCORAD) index. Our study strongly suggests that serum levels of Eotaxin-3/CCL26, but not of Eotaxin-2/CCL24, have a notable correlation with disease activity of AD and that Eotaxin-3/CCL26, as well as TARC/CCL17 and MDC/CCL22, may be involved in the pathogenesis of AD.

Bouchaib Lamkhioued - One of the best experts on this subject based on the ideXlab platform.

  • constitutive and cytokine stimulated expression of Eotaxin by human airway smooth muscle cells
    American Journal of Respiratory and Critical Care Medicine, 1999
    Co-Authors: Omar Ghaffar, Andrew D Luster, Qutayba Hamid, Paolo M Renzi, Zoulfia Allakhverdi, Sophie Molet, James C Hogg, Stephanie A Shore, Bouchaib Lamkhioued
    Abstract:

    Airway eosinophilia is a prominent feature of asthma that is believed to be mediated in part through the expression of specific chemokines such as Eotaxin, a potent eosinophil chemoattractant that is highly expressed by epithelial cells and inflammatory cells in asthmatic airways. Airway smooth muscle (ASM) has been identified as a potential source of cytokines and chemokines. The aim of the present study was to examine the capacity of human ASM to express Eotaxin. We demonstrate that airway myocytes constitutively express Eotaxin mRNA as detected by RT-PCR. Treatment of ASM for 24 h with different concentrations of TNF- α and IL-1 β alone or in combination enhanced the accumulation of Eotaxin transcripts. Maximal mRNA expression of Eotaxin was shown at 12 and 24 h following IL-1 β and TNF- α stimulation, respectively. The presence of immunoreactive Eotaxin was demonstrated by immunocytochemistry, and constitutive and cytokine-stimulated release of Eotaxin was confirmed in ASM culture supernatants by ELIS...

  • increased expression of Eotaxin in bronchoalveolar lavage and airways of asthmatics contributes to the chemotaxis of eosinophils to the site of inflammation
    Journal of Immunology, 1997
    Co-Authors: Bouchaib Lamkhioued, Andrew D Luster, Omar Ghaffar, Paolo M Renzi, Zoulfia Allakhverdi, E A Garciazepada, Sylvie Abiyounes, M D Rothenberg, Qutayba Hamid
    Abstract:

    Presently, there is considerable evidence for the participation of eosinophils in the pathophysiology of human bronchial asthma. Although increased numbers of eosinophils are present in the airways and bronchoalveolar lavage (BAL) fluid of atopic asthmatics, the mechanisms responsible for their preferential accumulation are still largely unknown. Eotaxin is a chemokine that promotes the selective recruitment of eosinophils. We report that atopic asthmatic patients have high concentrations of Eotaxin in BAL fluid and an increased expression of Eotaxin mRNA and protein in the epithelium and submucosa of their airways when compared with normal controls. In the BAL cells from asthmatic patients, Eotaxin immunoreactivity colocalized predominantly to macrophages (62.2%), with a lesser contribution from T cells (16.3%) and eosinophils (8.9%). BAL fluid from asthmatics contained chemotactic activity for eosinophils that was attributable in part to the presence of Eotaxin. Moreover, Eotaxin was more effective at inducing in vitro eosinophil chemotaxis when eosinophils were stimulated with IL-5 (a cytokine that enhances the effector capacity of mature eosinophils). These observations suggest that Eotaxin contributes to the pathogenesis of asthma by the specific recruitment of eosinophils into the airways.