Inflammatory Signalings Involved in Airway and Pulmonary Diseases

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.

Lipopolysaccharide induces ICAM-1 expression via a c-Src/NADPH oxidase/ROS-dependent NF-κB pathway in human pulmonary alveolar epithelial cells

“…#P Ͻ 0.01 compared with the cells transfected with Wt plasmid ϩ LPS (D). mal structure and function of the lung, as well as participating in pulmonary processes, such as inflammation (12). In our study, we established that LPS potentially enhanced ICAM-1 expression and THP-1 adhesion to HPAEpiCs.…”

“…c-Src is a member of the highly conserved Src family of nonreceptor tyrosine kinases, which display different expression patterns and have been implicated in numerous cellular processes, such as innate immune responses and signalings induced by cytokines, antigens, and growth factors (12,13). LPS has been shown to initiate c-Src activation in various cell types (12,13,18).…”

“…LPS induces ICAM-1 expression via PI3K/Akt. PI3K and Akt have been shown to mediate cellular activation, proliferation, and migration in various cell types, suggesting that they play critical roles in the development of inflammation (12). In this study, we investigated the roles of PI3K/Akt in LPSinduced ICAM-1 expression.…”

“…These results suggested that LPS-induced ICAM-1 expression is mediated through a c-Src/NADPH oxidase/ROS/EGFR and PDGFR/PI3K/Akt pathway in HPAEpiCs. (12). In this study, we investigated the role of NF-B in LPS-induced ICAM-1 expression.…”

Genomic instability in chronic airway inflammatory diseases

“…However, when this beneficial response occurs in an uncontrolled manner, it causes excessive cellular and tissue damage that results in chronic inflammation and destruction of normal tissue. [12,13] Since human airway is an open system, once exposed to cigarette smoke, gases, or other noxious particles, the epithelial cells are activated to produce inflammatory mediators. Reactive oxygen species (ROS) are one of the most important mediators.…”