Enhanced goblet cell hyperplasia in HDC knockout mice with allergic airway inflammation.

BACKGROUND Histamine is known to have immunoregulatory roles in allergic reactions through histamine receptor 1 (H1R), H2R, H3R and H4R. However, its role in goblet cell hyperplasia in the airways of asthma patients is yet to be clarified. OBJECTIVE This study was designed to examine the role of histamine in goblet cell hyperplasia using histamine-deficient mice (Hdc-/- mice) with allergic airway inflammation. METHODS Wild-type and Hdc-/- C57BL/6 mice were sensitized with ovalbumin (OVA). After a 2-week exposure to OVA, goblet cell hyperplasia was evaluated. Cell differentials and cytokines in BALF were analyzed. The mRNA levels of MUC5AC and Gob-5 gene were determined quantitatively. RESULTS The number of eosinophils in BALF increased in both the sensitized wild-type mice and Hdc-/- mice with OVA inhalation. In addition, the numbers of alveolar macrophages and lymphocytes in BALF increased significantly in the sensitized Hdc-/- mice with OVA inhalation compared to the wild-type mice under the same conditions. The concentrations of Interleukin-4 (IL-4), IL-5, IL-13, Interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and IL-2 in the BALF all increased significantly in both groups compared to those exposed to saline. In particular, the concentration of TNF-alpha in the Hdc-/- mice exposed to OVA was significantly higher than that in the wild-type mice under the same conditions. The mRNA levels of Gob-5 and MUC5AC, and the ratio of the goblet cells in the airway epithelium significantly increased in Hdc-/- mice exposed to OVA compared to wild-type mice. CONCLUSIONS These results suggested that histamine may play a regulatory role in goblet cell hyperplasia in allergic airway inflammation.

[1]  K. Yamauchi,et al.  Corrigendum: Enhanced Goblet Cell Hyperplasia in HDC Knockout Mice with Allergic Airway Inflammation [Allergol Int 2009;58:125-134] , 2009 .

[2]  R. Geha,et al.  The H1 histamine receptor regulates allergic lung responses. , 2006, The Journal of clinical investigation.

[3]  J. Voynow,et al.  Respiratory tract mucin genes and mucin glycoproteins in health and disease. , 2006, Physiological reviews.

[4]  S. Sealfon,et al.  Chronic exposure to TNF-alpha increases airway mucus gene expression in vivo. , 2005, The Journal of allergy and clinical immunology.

[5]  H. Stark,et al.  Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells 1 , 2005, The Journal of Immunology.

[6]  Q. Hamid,et al.  Niflumic acid and MSI-2216 reduce TNF-α–induced mucin expression in human airway mucosa , 2005 .

[7]  W. M. Foster,et al.  Neutrophil elastase induces mucus cell metaplasia in mouse lung. , 2004, American journal of physiology. Lung cellular and molecular physiology.

[8]  Y. Kato,et al.  Liver-Expressed Chemokine/CC Chemokine Ligand 16 Attracts Eosinophils by Interacting with Histamine H4 Receptor1 , 2004, The Journal of Immunology.

[9]  R. Thurmond,et al.  Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation , 2004, British journal of pharmacology.

[10]  A. Falus,et al.  Histamine deficiency in gene-targeted mice strongly reduces antigen-induced airway hyper-responsiveness, eosinophilia and allergen-specific IgE. , 2003, International immunology.

[11]  P. Desai,et al.  Histamine H4 Receptor Mediates Chemotaxis and Calcium Mobilization of Mast Cells , 2003, Journal of Pharmacology and Experimental Therapeutics.

[12]  D. Klinman,et al.  Cutting Edge: Histamine Inhibits IFN-α Release from Plasmacytoid Dendritic Cells , 2003, The Journal of Immunology.

[13]  K. Shirato,et al.  Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness. , 2003, American journal of respiratory and critical care medicine.

[14]  T. Yoshino,et al.  Histamine Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor-α Production in an Intercellular Adhesion Molecule-1- and B7.1-Dependent Manner , 2003, Journal of Pharmacology and Experimental Therapeutics.

[15]  D. Klinman,et al.  Cutting edge: histamine inhibits IFN-alpha release from plasmacytoid dendritic cells. , 2003, Journal of immunology.

[16]  T. Shibamoto,et al.  Enhancement of antigen-induced eosinophilic inflammation in the airways of mast-cell deficient mice by diesel exhaust particles. , 2002, Toxicology.

[17]  J. Fahy.  Goblet cell and mucin gene abnormalities in asthma. , 2002, Chest.

[18]  Y. Masuho,et al.  cDNA cloning and characterization of porcine histamine H4 receptor. , 2002, Biochimica et biophysica acta.

[19]  A. Nicholson,et al.  Expression of respiratory mucins in fatal status asthmaticus and mild asthma , 2002, Histopathology.

[20]  Minxue Huang,et al.  A calcium-activated chloride channel blocker inhibits goblet cell metaplasia and mucus overproduction. , 2002, Novartis Foundation symposium.

[21]  Marek Jutel,et al.  Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors , 2001, Nature.

[22]  G. Csaba,et al.  Mice lacking histidine decarboxylase exhibit abnormal mast cells , 2001, FEBS letters.

[23]  L. O’Neill.  Gob genes, mucus and asthma. , 2001, Trends in immunology.

[24]  L. O’Neill.  IL-1 versus TNF in arthritis? , 2001, Trends in immunology.

[25]  C. Bertrand,et al.  IL‐5 deficiency abolishes aspects of airway remodelling in a murine model of lung inflammation , 2001, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[26]  Yukio Fujisawa,et al.  Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[27]  R. Wu,et al.  Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression. , 2001, American journal of respiratory and critical care medicine.

[28]  N. Letwin,et al.  Muc-5/5ac mucin messenger RNA and protein expression is a marker of goblet cell metaplasia in murine airways. , 2000, American journal of respiratory cell and molecular biology.

[29]  S. Wenzel,et al.  Allergen-induced IL-9 directly stimulates mucin transcription in respiratory epithelial cells. , 1999, The Journal of clinical investigation.

[30]  K. Dabbagh,et al.  IL-4 induces mucin gene expression and goblet cell metaplasia in vitro and in vivo. , 1999, Journal of immunology.

[31]  R. Homer,et al.  Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. , 1999, The Journal of clinical investigation.

[32]  S. Sauleda,et al.  High-Throughput Real-Time Reverse Transcription-PCR Quantitation of Hepatitis C Virus RNA , 1999, Journal of Clinical Microbiology.

[33]  B. Vargaftig,et al.  Increased spontaneous release of tumour necrosis factor-alpha by alveolar macrophages from wheezy infants. , 1997, The European respiratory journal.

[34]  M. Jordana,et al.  Cytokine and eosinophil responses in the lung, peripheral blood, and bone marrow compartments in a murine model of allergen-induced airways inflammation. , 1997, American journal of respiratory cell and molecular biology.

[35]  R. Flavell,et al.  A novel role for murine IL-4 in vivo: induction of MUC5AC gene expression and mucin hypersecretion. , 1997, American journal of respiratory cell and molecular biology.

[36]  K. Livak,et al.  Real time quantitative PCR. , 1996, Genome research.

[37]  K. Shirato,et al.  Continuity of airway goblet cells and intraluminal mucus in the airways of patients with bronchial asthma. , 1996, The European respiratory journal.

[38]  A. James,et al.  Airway structure and inflammatory cells in fatal attacks of asthma. , 1996, The European respiratory journal.

[39]  R. Strieter,et al.  TNF-alpha mediates recruitment of neutrophils and eosinophils during airway inflammation. , 1995, Journal of immunology.

[40]  L. Laitinen,et al.  Pathology of asthma. , 1994, Allergy proceedings : the official journal of regional and state allergy societies.

[41]  J. Harkema,et al.  Ozone- and endotoxin-induced mucous cell metaplasias in rat airway epithelium: novel animal models to study toxicant-induced epithelial transformation in airways. , 1993, Toxicology letters.

[42]  A. Inglot,et al.  Elevated release of tumor necrosis factor-alpha and interferon-gamma by bronchoalveolar leukocytes from patients with bronchial asthma. , 1993, The American review of respiratory disease.

[43]  M. C. Liu,et al.  Analysis of cytokine transcripts in the bronchoalveolar lavage cells of patients with asthma. , 1993, American journal of respiratory cell and molecular biology.

[44]  A. Capron,et al.  Tumor necrosis factor alpha and interleukin-6 production by human mononuclear phagocytes from allergic asthmatics after IgE-dependent stimulation. , 1992, The American review of respiratory disease.

[45]  D. Broide,et al.  Cytokines in symptomatic asthma airways. , 1992, The Journal of allergy and clinical immunology.

[46]  M. Ebina,et al.  Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack. , 1992, Chest.

[47]  A. Capron,et al.  Increased secretion of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction. , 1991, The Journal of allergy and clinical immunology.

[48]  M. Mattei,et al.  Structure, mapping, and expression of fisp-12, a growth factor-inducible gene encoding a secreted cysteine-rich protein. , 1991, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[49]  P. Askenase,et al.  T-cell suppression and contrasuppression induced by histamine H2 and H1 receptor agonists, respectively. , 1982, Proceedings of the National Academy of Sciences of the United States of America.