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Inflammatory signalings involved in airway and pulmonary diseases.

Lee IT, Yang CM - Mediators Inflamm. (2013)

Bottom Line: Injuriously environmental stimuli can access the lung through either the airways or the pulmonary and systemic circulations.The time course and intensity of responses by resident and circulating cells may be regulated by various inflammatory signalings, including Src family kinases (SFKs), protein kinase C (PKC), growth factor tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)/reactive oxygen species (ROS), PI3K/Akt, MAPKs, nuclear factor-kappa B (NF-κB), activator protein-1 (AP-1), and other signaling molecules.Knowledge of the mechanisms of inflammation regulation could lead to the pharmacological manipulation of anti-inflammatory drugs in the respiratory diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthetics, Chang Gung Memorial Hospital at Linkuo and Chang Gung University, Kwei-San, Tao-Yuan 33302, Taiwan.

ABSTRACT
In respiratory diseases, there is an increased expression of multiple inflammatory proteins in the respiratory tract, including cytokines, chemokines, and adhesion molecules. Chemokines have been shown to regulate inflammation and immune cell differentiation. Moreover, many of the known inflammatory target proteins, such as matrix metalloproteinase-9 (MMP-9), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and cytosolic phospholipase A2 (cPLA2), are associated with airway and lung inflammation in response to various stimuli. Injuriously environmental stimuli can access the lung through either the airways or the pulmonary and systemic circulations. The time course and intensity of responses by resident and circulating cells may be regulated by various inflammatory signalings, including Src family kinases (SFKs), protein kinase C (PKC), growth factor tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)/reactive oxygen species (ROS), PI3K/Akt, MAPKs, nuclear factor-kappa B (NF-κB), activator protein-1 (AP-1), and other signaling molecules. These signaling molecules regulate both key inflammatory signaling transduction pathways and target proteins involved in airway and lung inflammation. Here, we discuss the mechanisms involved in the expression of inflammatory target proteins associated with the respiratory diseases. Knowledge of the mechanisms of inflammation regulation could lead to the pharmacological manipulation of anti-inflammatory drugs in the respiratory diseases.

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Related in: MedlinePlus

General overview of the inflammatory signaling pathways in respiratory diseases. Many of the known inflammatory target proteins, such as MMP-9, ICAM-1, VCAM-1, COX-2, and cPLA2, are associated with inflammatory signaling pathways induced by various stimuli, including TNF-α, IL-1β, ATP, cigarette smoke, LTA, or LPS. Moreover, the SFKs, PKCs, growth factor tyrosine kinase receptors, NADPH oxidase/ROS, PI3K/Akt, and MAPKs are components of signaling cascades that respond to extracellular stimuli by targeting transcription factors, such as NF-κB and AP-1, resulting in the modulation of inflammatory gene expression associated with pulmonary diseases.
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fig3: General overview of the inflammatory signaling pathways in respiratory diseases. Many of the known inflammatory target proteins, such as MMP-9, ICAM-1, VCAM-1, COX-2, and cPLA2, are associated with inflammatory signaling pathways induced by various stimuli, including TNF-α, IL-1β, ATP, cigarette smoke, LTA, or LPS. Moreover, the SFKs, PKCs, growth factor tyrosine kinase receptors, NADPH oxidase/ROS, PI3K/Akt, and MAPKs are components of signaling cascades that respond to extracellular stimuli by targeting transcription factors, such as NF-κB and AP-1, resulting in the modulation of inflammatory gene expression associated with pulmonary diseases.

Mentions: There is an increasing evidence that inflammatory proteins, such as VCAM-1, ICAM-1, cPLA2, COX-2, and MMP-9 are involved in the pathogenesis of respiratory diseases, such as asthma and COPD (Figure 3). Moreover, various inflammatory signaling pathways, including PKCs, NADPH oxidase/ROS, EGFR, PDGFR, c-Src, PI3K/Akt, MAPKs, AP-1, and NF-κB, are involved in the regulation of these inflammatory proteins (Figure 3). Further exploration of the role of VCAM-1, ICAM-1, cPLA2, COX-2, and MMP-9 in these highly prevalent diseases is crucial to identify which are possible therapeutic targets. The development of new inhibitors that are highly specific but have no major adverse effects is essential. As targeted delivery of inflammatory proteins inhibitors directly to the airway and lung might result in fewer side effects, this option should also be explored. Although the use of inhibitors of inflammatory signaling pathways in the treatment of respiratory diseases seems very attractive, further studies are needed to identify the exact role of inflammatory signaling molecules in these diseases and to develop highly specific inhibitors.


Inflammatory signalings involved in airway and pulmonary diseases.

Lee IT, Yang CM - Mediators Inflamm. (2013)

General overview of the inflammatory signaling pathways in respiratory diseases. Many of the known inflammatory target proteins, such as MMP-9, ICAM-1, VCAM-1, COX-2, and cPLA2, are associated with inflammatory signaling pathways induced by various stimuli, including TNF-α, IL-1β, ATP, cigarette smoke, LTA, or LPS. Moreover, the SFKs, PKCs, growth factor tyrosine kinase receptors, NADPH oxidase/ROS, PI3K/Akt, and MAPKs are components of signaling cascades that respond to extracellular stimuli by targeting transcription factors, such as NF-κB and AP-1, resulting in the modulation of inflammatory gene expression associated with pulmonary diseases.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3649692&req=5

fig3: General overview of the inflammatory signaling pathways in respiratory diseases. Many of the known inflammatory target proteins, such as MMP-9, ICAM-1, VCAM-1, COX-2, and cPLA2, are associated with inflammatory signaling pathways induced by various stimuli, including TNF-α, IL-1β, ATP, cigarette smoke, LTA, or LPS. Moreover, the SFKs, PKCs, growth factor tyrosine kinase receptors, NADPH oxidase/ROS, PI3K/Akt, and MAPKs are components of signaling cascades that respond to extracellular stimuli by targeting transcription factors, such as NF-κB and AP-1, resulting in the modulation of inflammatory gene expression associated with pulmonary diseases.
Mentions: There is an increasing evidence that inflammatory proteins, such as VCAM-1, ICAM-1, cPLA2, COX-2, and MMP-9 are involved in the pathogenesis of respiratory diseases, such as asthma and COPD (Figure 3). Moreover, various inflammatory signaling pathways, including PKCs, NADPH oxidase/ROS, EGFR, PDGFR, c-Src, PI3K/Akt, MAPKs, AP-1, and NF-κB, are involved in the regulation of these inflammatory proteins (Figure 3). Further exploration of the role of VCAM-1, ICAM-1, cPLA2, COX-2, and MMP-9 in these highly prevalent diseases is crucial to identify which are possible therapeutic targets. The development of new inhibitors that are highly specific but have no major adverse effects is essential. As targeted delivery of inflammatory proteins inhibitors directly to the airway and lung might result in fewer side effects, this option should also be explored. Although the use of inhibitors of inflammatory signaling pathways in the treatment of respiratory diseases seems very attractive, further studies are needed to identify the exact role of inflammatory signaling molecules in these diseases and to develop highly specific inhibitors.

Bottom Line: Injuriously environmental stimuli can access the lung through either the airways or the pulmonary and systemic circulations.The time course and intensity of responses by resident and circulating cells may be regulated by various inflammatory signalings, including Src family kinases (SFKs), protein kinase C (PKC), growth factor tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)/reactive oxygen species (ROS), PI3K/Akt, MAPKs, nuclear factor-kappa B (NF-κB), activator protein-1 (AP-1), and other signaling molecules.Knowledge of the mechanisms of inflammation regulation could lead to the pharmacological manipulation of anti-inflammatory drugs in the respiratory diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthetics, Chang Gung Memorial Hospital at Linkuo and Chang Gung University, Kwei-San, Tao-Yuan 33302, Taiwan.

ABSTRACT
In respiratory diseases, there is an increased expression of multiple inflammatory proteins in the respiratory tract, including cytokines, chemokines, and adhesion molecules. Chemokines have been shown to regulate inflammation and immune cell differentiation. Moreover, many of the known inflammatory target proteins, such as matrix metalloproteinase-9 (MMP-9), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and cytosolic phospholipase A2 (cPLA2), are associated with airway and lung inflammation in response to various stimuli. Injuriously environmental stimuli can access the lung through either the airways or the pulmonary and systemic circulations. The time course and intensity of responses by resident and circulating cells may be regulated by various inflammatory signalings, including Src family kinases (SFKs), protein kinase C (PKC), growth factor tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)/reactive oxygen species (ROS), PI3K/Akt, MAPKs, nuclear factor-kappa B (NF-κB), activator protein-1 (AP-1), and other signaling molecules. These signaling molecules regulate both key inflammatory signaling transduction pathways and target proteins involved in airway and lung inflammation. Here, we discuss the mechanisms involved in the expression of inflammatory target proteins associated with the respiratory diseases. Knowledge of the mechanisms of inflammation regulation could lead to the pharmacological manipulation of anti-inflammatory drugs in the respiratory diseases.

Show MeSH
Related in: MedlinePlus