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Featured researches published by Yuehua Li.


Nature Medicine | 2004

A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma

Monique Singer; Linda D. Martin; B. Boris Vargaftig; Joungjoa Park; Achim D Gruber; Yuehua Li; Kenneth B. Adler

Mucus hypersecretion is a crucial feature of pulmonary diseases such as asthma, chronic bronchitis and cystic fibrosis. Despite much research, there is still no effective therapy for this condition. Recently, we showed that the myristoylated, alanine-rich C-kinase substrate (MARCKS) protein is required for mucus secretion by human bronchial epithelial cells in culture. Having synthesized a peptide corresponding to the N-terminal domain of MARCKS, we now show that the intratracheal instillation of this peptide blocks mucus hypersecretion in a mouse model of asthma. A missense peptide with the same amino acid composition has no effect. Based on quantitative histochemical analysis of the mouse airways, the peptide seems to act by blocking mucus release from goblet cells, possibly by inhibiting the attachment of MARCKS to membranes of intracellular mucin granules. These results support a pivotal role for MARCKS protein, specifically its N-terminal region, in modulating this secretory process in mammalian airways. Intratracheal administration of this MARCKS-related peptide could therapeutically reduce mucus secretion in the airways of human patients with asthma, chronic bronchitis and cystic fibrosis.


American Journal of Pathology | 2005

Human neutrophil elastase induces hypersecretion of mucin from well-differentiated human bronchial epithelial cells in vitro via a protein kinase Cδ-mediated mechanism

Jin-Ah Park; Fang He; Linda D. Martin; Yuehua Li; Brian N. Chorley; Kenneth B. Adler

The presence of mucus obstruction and neutrophil-predominant inflammation in several lung disorders, such as cystic fibrosis, suggests a relationship between neutrophils and excess mucus production. Mechanisms of human neutrophil elastase (HNE)-induced mucin secretion by well-differentiated normal human bronchial epithelial (NHBE) cells maintained in air/liquid interface culture were investigated. HNE increased mucin secretion in a concentration-dependent manner, with maximal stimulation (more than twofold) occurring within a short (15 minutes) time period. Mucins MUC 5 AC and MUC 5 B, but not MUC 2, were released in response to HNE. Stimulation of mucin secretion required partial elastase enzymatic activity and did not appear to involve a soluble product released by the cells. HNE-stimulated secretion involved activation of protein kinase C (PKC), as HNE exposure rapidly provoked PKC enzymatic activity that was attenuated by the general PKC inhibitors calphostin C and bisindoylmaleimide I. Of the different isoforms, PKCalpha, delta, zeta, lambda, iota, and epsilon were constitutively expressed in NHBE cells while PKCbeta, eta, and mu were PMA-inducible. PKCdelta was the only isoform to translocate from cytoplasm to membrane in response to HNE. Inhibition of PKCdelta attenuated HNE-mediated mucin secretion. The results suggest HNE stimulation of mucin release by human airway epithelial cells involves intracellular activation of PKC, specifically the delta isoform.


Respiratory Research | 2006

Differential Muc2 and Muc5ac secretion by stimulated guinea pig tracheal epithelial cells in vitro

Brian N. Chorley; Anne L. Crews; Yuehua Li; Kenneth B. Adler; Michael Minnicozzi; Linda D. Martin

BackgroundMucus overproduction is a characteristic of inflammatory pulmonary diseases including asthma, chronic bronchitis, and cystic fibrosis. Expression of two mucin genes, MUC2 and MUC5AC, and their protein products (mucins), is modulated in certain disease states. Understanding the signaling mechanisms that regulate the production and secretion of these major mucus components may contribute significantly to development of effective therapies to modify their expression in inflamed airways.MethodsTo study the differential expression of Muc2 and Muc5ac, a novel monoclonal antibody recognizing guinea pig Muc2 and a commercially-available antibody against human MUC5AC were optimized for recognition of specific guinea pig mucins by enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemistry (IHC). These antibodies were then used to analyze expression of Muc2 and another mucin subtype (likely Muc5ac) in guinea pig tracheal epithelial (GPTE) cells stimulated with a mixture of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and interferon- γ (IFN-γ)].ResultsThe anti-Muc2 (C4) and anti-MUC5AC (45M1) monoclonal antibodies specifically recognized proteins located in Muc2-dominant small intestinal and Muc5ac-dominant stomach mucosae, respectively, in both Western and ELISA experimental protocols. IHC protocols confirmed that C4 recognizes murine small intestine mucosal proteins while 45M1 does not react. C4 and 45M1 also stained specific epithelial cells in guinea pig lung sections. In the resting state, Muc2 was recognized as a highly expressed intracellular mucin in GPTE cells in vitro. Following cytokine exposure, secretion of Muc2, but not the mucin recognized by the 45M1 antibody (likely Muc5ac), was increased from the GPTE cells, with a concomitant increase in intracellular expression of both mucins.ConclusionGiven the tissue specificity in IHC and the differential hybridization to high molecular weight proteins by Western blot, we conclude that the antibodies used in this study can recognize specific mucin subtypes in guinea pig airway epithelium and in proteins from GPTE cells. In addition, Muc2 is highly expressed constitutively, modulated by inflammation, and secreted differentially (as compared to Muc5ac) in GPTE cells. This finding contrasts with expression patterns in the airway epithelium of a variety of mammalian species in which only Muc5ac predominates.


Journal of Biological Chemistry | 2001

MARCKS Protein Is a Key Molecule Regulating Mucin Secretion by Human Airway Epithelial Cells in Vitro

Yuehua Li; Linda D. Martin; Gwendolyn Spizz; Kenneth B. Adler


Toxicology and Applied Pharmacology | 2000

Residual Oil Fly Ash Induces Cytotoxicity and Mucin Secretion by Guinea Pig Tracheal Epithelial Cells via an Oxidant-Mediated Mechanism

Nanfei Jiang; Kevin L. Dreher; Janice A. Dye; Yuehua Li; Judy H. Richards; Linda D. Martin; Kenneth B. Adler


American Journal of Respiratory Cell and Molecular Biology | 2001

Airway epithelium and mucus: intracellular signaling pathways for gene expression and secretion.

Kenneth B. Adler; Yuehua Li


American Journal of Respiratory Cell and Molecular Biology | 2001

Enhanced Expression of Mucin Genes in a Guinea Pig Model of Allergic Asthma

Yuehua Li; Linda D. Martin; Michael Minnicozzi; Scott Greenfeder; Jennifer Fine; Carol A. Pettersen; Brian N. Chorley; Kenneth B. Adler


The International Journal of Biochemistry & Cell Biology | 2008

Protease-activated receptor-2 (PAR-2) is a weak enhancer of mucin secretion by human bronchial epithelial cells in vitro

Ko-Wei Lin; Joungjoa Park; Anne L. Crews; Yuehua Li; Kenneth B. Adler


American Journal of Respiratory Cell and Molecular Biology | 2006

(R)-albuterol elicits antiinflammatory effects in human airway epithelial cells via iNOS

Brian N. Chorley; Yuehua Li; Shijing Fang; Jin-Ah Park; Kenneth B. Adler


Archive | 2007

Methods for regulating inflammatory mediators and peptides useful therein

Shuji Takashi; Indu Parikh; Kenneth B. Adler; Linda D. Martin; Yuehua Li

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Kenneth B. Adler

North Carolina State University

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Linda D. Martin

North Carolina State University

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Brian N. Chorley

North Carolina State University

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Kinda D. Martin

North Carolina State University

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Anne L. Crews

North Carolina State University

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Joungjoa Park

North Carolina State University

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Indu Parikh

University of Pennsylvania

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