Regulation of TNF‐α and IFN‐γ induced CXCL10 expression: participation of the airway smooth muscle in the pulmonary inflammatory response in chronic obstructive pulmonary disease

2003 ◽  
Vol 18 (1) ◽  
pp. 191-193 ◽  
Author(s):  
Elizabeth L. Hardaker ◽  
Alicia M. Bacon ◽  
Karey Carlson ◽  
Amy K. Roshak ◽  
James J. Foley ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Smooth Muscle ◽  
Inflammatory Response ◽  
Pulmonary Disease ◽  
Airway Smooth Muscle ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Tnf Α ◽  
Pulmonary Inflammatory Response ◽  
Ifn Γ

Platelet-Derived Growth Factors (PDGFs) are Key Players in the Stimulation of Airway Smooth Muscle Cells (ASMCs) Alteration in Asthma and Chronic Obstructive Pulmonary Disease (COPD) with Multifarious Inhibitors at an Early Stage of Development

2020 ◽  
Vol 17 (4) ◽  
pp. 324-332
Author(s):  
Xiaodong Shi ◽  
Kwaku Appiah-Kubi
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Smooth Muscle ◽  
Growth Factors ◽  
Smooth Muscle Cells ◽  
Pulmonary Disease ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Chronic Obstructive ◽  
Airway Smooth Muscle Cells ◽  
Obstructive Pulmonary Disease

Background: Alterations in airway smooth muscle cells cause an increase in their mass and result in a significant impact on airway remodeling diseases such as asthma and chronic obstructive pulmonary disease. Several studies have used platelet-derived growth factors to stimulate the alterations of airway smooth muscle cells. Objective: This review discusses the platelet-derived growth factor-stimulated alterations of airway smooth muscle cells, diversity of inhibitors and inhibitory actions against these alterations and their related mechanisms, and how this diversity presents an avenue for the development of multifarious therapeutic targets for airway remodeling diseases especially asthma and chronic obstructive pulmonary disease. Methods: A comprehensive search of PubMed and Medscape database for studies that investigated the stimulation of the alterations of airway smooth muscle cells in asthma and chronic obstructive pulmonary disease by platelet-derived growth factors and inhibitions of these alterations. Results: Marked platelet-derived growth factor-stimulated alterations of airway smooth muscle cells are proliferation, migration and proliferative phenotype with diverse inhibitors and inhibitory actions against these alterations. Inhibitory actions are the result of the activation of protein kinase, overexpression of Tripartite motif protein, human transporter sub-family ABCA1 protein and miRNAs, knockdown of an isoform of reticulon 4 and follistatin protein, exogenous applications of recombinant proteins, supplements and active metabolite of retinoic acid, flavonoid extracts and polysaccharides extract. Conclusion: The multifarious inhibitors and inhibitory actions with varied mechanisms in platelet-derived growth factors-stimulated alterations of airway smooth muscle cells present a potential for diverse therapeutic targets for the treatment of airway remodeling diseases.

scholarly journals Apoptosis signal-regulating kinase 1 inhibition attenuates human airway smooth muscle growth and migration in chronic obstructive pulmonary disease

2018 ◽  
Vol 132 (14) ◽  
pp. 1615-1627 ◽  
Author(s):  
Mathew S. Eapen ◽  
Anudeep Kota ◽  
Howard Vindin ◽  
Kielan D. McAlinden ◽  
Dia Xenaki ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Smooth Muscle ◽  
Pulmonary Disease ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Mitogen Activated Protein Kinase ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

Increased airway smooth muscle (ASM) mass is observed in chronic obstructive pulmonary disease (COPD), which is correlated with disease severity and negatively affects lung function in these patients. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) activated by various stress stimuli, including reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and is known to regulate cell proliferation. ASM cells from COPD patients are hyperproliferative to mitogens in vitro. However, the role of ASK1 in ASM growth is not established. Here, we aim to determine the effects of ASK1 inhibition on ASM growth and pro-mitogenic signaling using ASM cells from COPD patients. We found greater expression of ASK1 in ASM bundles of COPD lung when compared with non-COPD. Pre-treatment of ASM cells with highly selective ASK1 inhibitor, TC ASK 10 resulted in a dose-dependent reduction in mitogen (FBS, PDGF, and EGF; 72 h)-induced ASM growth as measured by CyQUANT assay. Further, molecular targetting of ASK1 using siRNA in ASM cells prevented mitogen-induced cell growth. In addition, to anti-mitogenic potential, ASK1 inhibitor also prevented TGFβ1-induced migration of ASM cells in vitro. Immunoblotting revealed that anti-mitogenic effects are mediated by C-Jun N-terminal kinase (JNK) and p38MAP kinase-signaling pathways as evident by reduced phosphorylation of downstream effectors JNK1/2 and p38MAP kinases, respectively, with no effect on extracellular signal-regulated kinase (ERK) 1/2 (ERK1/2). Collectively, these findings establish the anti-mitogenic effect of ASK1 inhibition and identify a novel pathway that can be targetted to reduce or prevent excessive ASM mass in COPD.

Constitutive and inducible thymic stromal lymphopoietin expression in human airway smooth muscle cells: role in chronic obstructive pulmonary disease

2007 ◽  
Vol 293 (2) ◽  
pp. L375-L382 ◽  
Author(s):  
Keqin Zhang ◽  
Lianyu Shan ◽  
Muhammad Sahidu Rahman ◽  
Helmut Unruh ◽  
Andrew J. Halayko ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Inflammation ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
Obstructive Pulmonary Disease ◽  
Tnf Α

Thymic stromal lymphopoietin (TSLP) is a novel cytokine that triggers dendritic cell-mediated T helper (Th)-2 inflammatory responses. Previous studies have demonstrated that human airway smooth muscle cells (HASMC) play a critical role in initiating or perpetuating airway inflammation by producing chemokines and cytokines. In this study, we first evaluated the expression of TSLP in primary HASMC and investigated how proinflammatory cytokines (TNF-α and IL-1β) and Th-2 cytokines (IL-4, IL-9) regulate TSLP production from HASMC. TSLP mRNA and protein were assessed by real-time RT-PCR, ELISA, and immunofluorescence from primary HASMC cultures. Primary HASMC express constitutive level of TSLP. Incubation of HASMC with IL-1 or TNF-α resulted in a significant increase of TSLP mRNA and protein release from HASMC. Furthermore, combination of IL-1β and TNF-α has an additive effect on TSLP release by HASMC. Primary HASMC pretreated with inhibitors of p38 or p42/p44 ERK MAPK, but not phosphatidylinositol 3-kinase, showed a significant decrease in TSLP release on IL-1β and TNF-α treatment. Furthermore, TSLP immunoreactivity was present in ASM bundle from chronic obstructive pulmonary disease (COPD) and to lesser degree in normal subjects. Taken together, our data provide the first evidence of IL-1β- and TNF-α-induced TSLP expression in HASMC via (p38, p42/p44) MAPK signaling pathways. Our results raise the possibility that HASMC may play a role in COPD airway inflammation via TSLP-dependent pathway.

scholarly journals Change of Serum Inflammatory Cytokines Levels in Patients With Chronic Obstructive Pulmonary Disease, Pneumonia and Lung Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382095180
Author(s):  
Jian Chen ◽  
Xincai Li ◽  
ChaoLin Huang ◽  
Ying Lin ◽  
Qingfu Dai
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Inflammatory Cytokines ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Cancer Group ◽  
Tnf Α ◽  
Ifn Γ

Objective: This study aimed to investigate the serum inflammatory cytokines levels in patients with COPD, pneumonia and lung cancer, and assess the correlation between the levels of inflammatory cytokines levels and development of these diseases. Methods: Two hundred thirty-two patients including 114 patients with pneumonia, 76 patients with chronic obstructive pulmonary disease (COPD) and 42 patients with lung cancer, and 62 age-matched healthy volunteers as controls were enrolled. The pro-inflammatory cytokine IL-6, IL-2, IFN-γ, TNF-α, anti-inflammatory cytokines IL-4 and IL-10 in serum were analyzed by flow cytometry microsphere array (CBA). Results: We found that the levels of TNF-α and IL-10 in patients with lung cancer, COPD and pneumonia were significantly higher than control group. The IL-6 in the lung cancer group were significantly increased compared with the controls and COPD group, pneumonia group. IFN-γ and IL-2 levels were lower in lung cancer compared with controls and COPD group, pneumonia group. TNF-α, IL-4 and IL-10 levels were increased in patients with COPD and pneumonia compared with controls. In addition, the concentrations of IFN-γ and IL-6 were increased in acute exacerbation COPD (AECOPD) group compared with stable COPD group. Conclusion: In conclusion, elevated TNF-α and IL-10 levels in serum may be related with lung diseases including lung cancer, COPD and pneumonia. Additionally, IFN-γ and IL-6 might be potential biomarkers for the further deterioration of lung disease patients. The increased concentrations of IFN-γ and IL-6 might be used to predict the exacerbation of COPD.

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