A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma

Toda, Masao; Tulic, Meri K.; Levitt, Roy C.; Hamid, Qutayba

doi:10.1067/mai.2002.121555

Cited by 117 publications

(87 citation statements)

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“…Whether the secretion of the ovine CLCA protein has a direct or indirect function in worm expulsion remains unknown, although hCLCA1 has been associated with an increase in mucus production following a Th2 response of the respiratory tract [34]. Furthermore, increased expression of IL-9 resulted in increased expression of hCLCA1 mRNA by epithelial cells in patients suffering from asthma [31] suggesting that hCLCA1 may be responsible at least in part for the overproduction of mucus by the asthmatic patients. Increased volume or viscosity of mucus may result in entrapment of infective larvae and thus reduced establishment in tissues that have been previously challenged with the parasite.…”

Section: Discussionmentioning

confidence: 99%

Proteomic approach to identify candidate effector molecules during the in vitro immune exclusion of infectiveTeladorsagia circumcinctain the abomasum of sheep

Athanasiadou

Pemberton²,

Jackson³

et al. 2008

Vet. Res.

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-In the present study we have employed an in vitro organ challenge model to study the post-challenge responses in parasite naïve and immune gastric tissue of sheep, in an attempt to identify the host derived factors involved in immune exclusion of Teladorsagia circumcincta larvae. Proteins present in the epithelial cells and mucus from ovine abomasa following parasite challenge in previously naïve and immune animals were analysed through Matrix Assisted Laser Desorption/Ionization-Time of Flight (MALDI-Tof)-MS and shotgun proteomics. MALDI-ToF analysis of epithelial cell lysates revealed that a number of proteins identified were differentially expressed in naïve and immune cells. These included intelectin and lysozymes, which were present at higher levels in epithelial cell lysates derived from immune samples. A large number of proteins were identified in the mucosal wash from immune tissue which were not present in the mucosal wash of the naïve tissue. Some of these proteins were present in washes of immune tissue prior to the parasite challenge including immunoglobulin A, galectin 14 and 15 and sheep mast cell protease 1. However, other proteins, such as calcium activated chloride channel and intelectin were only detected in the washings from the challenged tissue. The latter may be related to an enhanced mucus release, which may result in entrapment of infective larvae and thus reduced establishment in tissue that has been previously challenged with the parasite. In conclusion, several proteins have been identified which may be involved, either directly or indirectly, in the exclusion and immune elimination of incoming infective larvae. In the present study, the usefulness of the in vitro model has been confirmed, and the global proteomic approach has identified proteins that had not previously been associated with parasite exclusion from abomasal mucosa, such as the calcium activated chloride channel.immunity / mucus / proteomics / sheep / Teladorsagia circumcincta

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Section: Discussionmentioning

confidence: 99%

Proteomic approach to identify candidate effector molecules during the in vitro immune exclusion of infectiveTeladorsagia circumcinctain the abomasum of sheep

Athanasiadou

Pemberton²,

Jackson³

et al. 2008

Vet. Res.

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“…IL-13 induces not only MUC5AC gene expression leading to mucin synthesis, a defining characteristic of the goblet cell phenotype, but also induces other genes, some of which are important for goblet cell function, including the genes for the CaCC1, and the trefoil factor family (TFF),which will be mentioned later [34,35]. In addition, Young et al [36] indicated that up-regulated Muc5AC expression is the central event in goblet cell metaplasia in antigen-challenged mice.…”

Section: Goblet Cell Metaplasia From Clara and Ciliated Cellsmentioning

confidence: 99%

Molecular Mechanisms of Metaplasia, Differentiation and Hyperplasia of Goblet Cellin Allergic Asthma

Hayashi¹

2012

J Aller Ther

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Bronchial allergic asthma (asthma) is an airway inflammation characterized by airflow obstruction of variable degrees with bronchial hyper-responsiveness and is induced by a complex interaction of environmental and genetic factors. Asthma of the human can be divided into an immediate-and a late-phase reaction, and some of the patients develop a late-phase reaction after a symptom-free interval. Hallmarks of asthma are mucus overproduction by goblet cells associated with responses of helper T(Th)2 cells. Mucus hypersecretion from goblet cells themselves or by metaplasia and/or hyperplasia of goblet cells appears to be associated with disease severity in asthma, because mucus production by those cells in local bronchial-bronchiolar lesions causes airway mucus plugging. However, the mechanisms of mucus production are not fully understood. Molecular mechanisms of goblet cell metaplasia, differentiation and hyperplasia will be reviewed in this article. Also, the relationship between allergic inflammation in Th1/Th2 paradigm shift and thymic stromal lymphopoietin (TSLP) was included for the understanding of goblet cell response in asthma. The clarification of mechanisms of mucin production in vivo may lead to the development of novel therapeutic strategies to suppress mucus production in asthma.

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“…Interleukin-13, a cytokine involved in the pathogenesis of asthma, enhances the calcium-activated chloride conductance in human bronchial epithelial cells (30), and hCLCA1 expression is likewise up-regulated in patients with bronchial asthma (31,32). Overexpression of interleukin-9 in transgenic mice results in the induction of mCLCA3 in lung epithelium and an asthma phenotype (30,33).…”

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confidence: 99%

Molecular and Functional Analyses of Two New Calcium-activated Chloride Channel Family Members from Mouse Eye and Intestine

Evans

Thoreson

Beck

2004

Journal of Biological Chemistry

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Two new calcium-activated chloride channel (CLCA) family members, mCLCA5 and mCLCA6, have been cloned from mouse eye and intestine, respectively. mCLCA5 is highly homologous to hCLCA2, and mCLCA6 is highly homologous to hCLCA4. mCLCA5 is widely expressed with strong expression in eye and spleen, whereas mCLCA6 is primarily expressed in intestine and stomach. mCLCA6 is also expressed as a splice variant lacking exon 8 and part of exon 10 in intestine and stomach. Transfection of tsA201 cells with enhanced green fluorescent protein-tagged versions of the three cDNAs reveals protein products of 155 and 65 kDa for mCLCA5 and mCLCA6 and 145 and 65 kDa for the mCLCA6 splice variant. In vitro translation of mCLCA5 generates a 90-kDa protein that does not appear to be glycosylated. mCLCA6 also generates a 90-kDa protein that is glycosylated to a 110-kDa product, whereas the mCLCA6 splice variant generates an 80-kDa product that is 100 kDa after glycosylation. Treatment of enhanced green fluorescent protein-tagged mCLCA6 with PNGase F (peptide: N-glycosidase F) to remove N-linked glycosyl groups shows a reduction in size of the 65 kDa product to 60 kDa. Consistent with the hypothesis that mCLCA5, mCLCA6, and its splice variant encode calcium-activated chloride channels, in HEK293 cells expressing CLCAs ionomycin-evoked increases in intracellular calcium stimulated a current that reversed near Cl ؊ equilibrium potential, E Cl . Furthermore, these currents were inhibited by the chloride channel blocker niflumic acid. Given the prominent role of hCLCA2 in cancer cell adhesion and the unique high level of expression of hCLCA4 in brain, the identification of their murine counterparts presents the opportunity to clarify the role of CLCAs in disease and normal cell physiology.Calcium-activated chloride currents have been characterized physiologically in many cell types including epithelium (1-4), smooth muscle (5-7), skeletal muscle (8), and neurons (9, 10). However, the molecular identities of channels responsible for calcium-activated chloride currents have not been determined.Proteins of the bestrophin and CLCA 1 families have been proposed to function as calcium-activated chloride channels (11)(12)(13)(14)(15)(16)(17)(18)(19).The CLCA gene family encodes proteins with four or five putative transmembrane domains, and many family members appear to function as calcium-activated chloride channels (bCLCA1, mCLCA1, mCLCA4, hCLCA1, and hCLCA2) (15)(16)(17)(18)(19). Other studies suggest that CLCAs may not be chloride channels themselves but may instead modulate chloride channels (20,21) In addition to their potential roles as ion channels or regulators of ion channels, some CLCA family members function as adhesion molecules. For example, bCLCA2 (Lu-ECAM-1), mCLCA1, and hCLCA2 all appear to be cell-cell adhesion molecules that help mediate the colonization of lung by lung metastatic murine B16-F10 melanoma cells (22-24). ␤ 4 integrin expressed on the surface of these melanoma cells can adhere to mCLCA1 in lung endothelium. This lea...

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A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma

Cited by 117 publications

References 23 publications

Proteomic approach to identify candidate effector molecules during the in vitro immune exclusion of infectiveTeladorsagia circumcinctain the abomasum of sheep

Proteomic approach to identify candidate effector molecules during the in vitro immune exclusion of infectiveTeladorsagia circumcinctain the abomasum of sheep

Molecular Mechanisms of Metaplasia, Differentiation and Hyperplasia of Goblet Cellin Allergic Asthma

Molecular and Functional Analyses of Two New Calcium-activated Chloride Channel Family Members from Mouse Eye and Intestine

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