BIOMAT Database Logo BIOMAT Database Logo

Effect of epithelial-specific MyD88 signaling pathway on airway inflammatory response to organic dust exposure. 2023

Amber N Johnson, and John Dickinson, and Amy Nelson, and Rohit Gaurav, and Katrina Kudrna, and Scott E Evans, and Katherine Janike, and Todd A Wyatt, and Jill A Poole
Department of Internal Medicine, Pulmonary Critical Care and Sleep Division, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.

The Toll-like receptor (TLR) adaptor protein MyD88 is integral to airway inflammatory response to microbial-enriched organic dust extract (ODE) exposures. ODE-induced airway neutrophil influx and release of pro-inflammatory cytokines was essentially abrogated in global MyD88-deficient mice, yet these mice demonstrate an increase in airway epithelial cell mucin expression. To further elucidate the role of MyD88-dependent responses specific to lung airway epithelial cells in response to ODE in vivo, the surfactant protein C protein (SPC) Cre+ embryologic expressing airway epithelial cells floxed for MyD88 to disrupt MyD88 signaling were utilized. The inducible club cell secretory protein (CCSP) Cre+, MyD88 floxed, were also developed. Using an established protocol, mice were intranasally instilled with ODE or saline once or daily up to 3 weeks. Mice with MyD88-deficient SPC+ lung epithelial cells exhibited decreased neutrophil influx following ODE exposure once and repetitively for 1 week without modulation of classic pro-inflammatory mediators including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and neutrophil chemoattractants. This protective response was lost after 3 weeks of repetitive exposure. ODE-induced Muc5ac mucin expression at 1 week was also reduced in MyD88-deficient SPC+ cells. Acute ODE-induced IL-33 was reduced in MyD88-deficient SPC+ cells whereas serum IgE levels were increased at one week. In contrast, mice with inducible MyD88-deficient CCSP+ airway epithelial cells demonstrated no significant difference in experimental indices following ODE exposure. Collectively, these findings suggest that MyD88-dependent signaling targeted to all airway epithelial cells plays an important role in mediating neutrophil influx and mucin production in response to acute organic dust exposures.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009077 Mucins High molecular weight mucoproteins that protect the surface of EPITHELIAL CELLS by providing a barrier to particulate matter and microorganisms. Membrane-anchored mucins may have additional roles concerned with protein interactions at the cell surface. Mucin
D004391 Dust Earth or other matter in fine, dry particles. (Random House Unabridged Dictionary, 2d ed) House Dust,Housedust,Dust, House
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015850 Interleukin-6 A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS. Hepatocyte-Stimulating Factor,Hybridoma Growth Factor,IL-6,MGI-2,Myeloid Differentiation-Inducing Protein,Plasmacytoma Growth Factor,B Cell Stimulatory Factor-2,B-Cell Differentiation Factor,B-Cell Differentiation Factor-2,B-Cell Stimulatory Factor 2,B-Cell Stimulatory Factor-2,BSF-2,Differentiation Factor, B-Cell,Differentiation Factor-2, B-Cell,IFN-beta 2,IL6,Interferon beta-2,B Cell Differentiation Factor,B Cell Differentiation Factor 2,B Cell Stimulatory Factor 2,Differentiation Factor 2, B Cell,Differentiation Factor, B Cell,Differentiation-Inducing Protein, Myeloid,Growth Factor, Hybridoma,Growth Factor, Plasmacytoma,Hepatocyte Stimulating Factor,Interferon beta 2,Interleukin 6,Myeloid Differentiation Inducing Protein,beta-2, Interferon
D051193 Toll-Like Receptors A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS. Receptors, Toll-Like,Toll-Like Receptor,Receptor, Toll-Like,Receptors, Toll Like,Toll Like Receptor,Toll Like Receptors
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D053594 Myeloid Differentiation Factor 88 An intracellular signaling adaptor protein that plays a role in TOLL-LIKE RECEPTOR and INTERLEUKIN 1 RECEPTORS signal transduction. It forms a signaling complex with the activated cell surface receptors and members of the IRAK KINASES. MyD88 Protein,TLR Signal Adaptor Protein MyD88,Toll-Like Receptor Signal Adaptor Protein MyD88,Toll Like Receptor Signal Adaptor Protein MyD88

Related Publications

Amber N Johnson, and John Dickinson, and Amy Nelson, and Rohit Gaurav, and Katrina Kudrna, and Scott E Evans, and Katherine Janike, and Todd A Wyatt, and Jill A Poole
The effect of fluticasone on the airway inflammatory response to organic dust.
October 2004, The European respiratory journal,
Amber N Johnson, and John Dickinson, and Amy Nelson, and Rohit Gaurav, and Katrina Kudrna, and Scott E Evans, and Katherine Janike, and Todd A Wyatt, and Jill A Poole
MyD88 controls airway epithelial Muc5ac expression during TLR activation conditions from agricultural organic dust exposure.
February 2019, American journal of physiology. Lung cellular and molecular physiology,
Amber N Johnson, and John Dickinson, and Amy Nelson, and Rohit Gaurav, and Katrina Kudrna, and Scott E Evans, and Katherine Janike, and Todd A Wyatt, and Jill A Poole
Mycoplasma ovipneumoniae induces inflammatory response in sheep airway epithelial cells via a MyD88-dependent TLR signaling pathway.
January 2015, Veterinary immunology and immunopathology,
Amber N Johnson, and John Dickinson, and Amy Nelson, and Rohit Gaurav, and Katrina Kudrna, and Scott E Evans, and Katherine Janike, and Todd A Wyatt, and Jill A Poole
Effect of exposure to volatile organic compounds (VOCs) on airway inflammatory response in mice.
January 2012, The Journal of toxicological sciences,
Amber N Johnson, and John Dickinson, and Amy Nelson, and Rohit Gaurav, and Katrina Kudrna, and Scott E Evans, and Katherine Janike, and Todd A Wyatt, and Jill A Poole
MyD88 in lung resident cells governs airway inflammatory and pulmonary function responses to organic dust treatment.
September 2015, Respiratory research,
Amber N Johnson, and John Dickinson, and Amy Nelson, and Rohit Gaurav, and Katrina Kudrna, and Scott E Evans, and Katherine Janike, and Todd A Wyatt, and Jill A Poole
Pre-exposure to hydrogen sulfide modulates the innate inflammatory response to organic dust.
April 2021, Cell and tissue research,
Amber N Johnson, and John Dickinson, and Amy Nelson, and Rohit Gaurav, and Katrina Kudrna, and Scott E Evans, and Katherine Janike, and Todd A Wyatt, and Jill A Poole
Organic dust exposure and chronic airway disease.
October 1996, American journal of respiratory and critical care medicine,
Amber N Johnson, and John Dickinson, and Amy Nelson, and Rohit Gaurav, and Katrina Kudrna, and Scott E Evans, and Katherine Janike, and Todd A Wyatt, and Jill A Poole
Maresin-1 reduces the pro-inflammatory response of bronchial epithelial cells to organic dust.
May 2013, Respiratory research,
Amber N Johnson, and John Dickinson, and Amy Nelson, and Rohit Gaurav, and Katrina Kudrna, and Scott E Evans, and Katherine Janike, and Todd A Wyatt, and Jill A Poole
Exposure to hog barn dust alters airway epithelial ciliary beating.
June 2008, The European respiratory journal,
Amber N Johnson, and John Dickinson, and Amy Nelson, and Rohit Gaurav, and Katrina Kudrna, and Scott E Evans, and Katherine Janike, and Todd A Wyatt, and Jill A Poole
Euxanthone inhibits lipopolysaccharide-induced injury, inflammatory response, and MUC5AC hypersecretion in human airway epithelial cells by the TLR4/MyD88 pathway.
April 2022, Journal of applied toxicology : JAT,
Copied contents to your clipboard!