Upregulation of ICAM-1 and IL-1β protein expression promotes lung injury in chronic obstructive pulmonary disease

Abstract

ABSTRACT. Chronic obstructive pulmonary disease (COPD) is a devastating lung disorder characterized by sustained airway flow restriction that is not fully reversible. The precise pathogenic mechanisms are unknown, but it is clear that cigarette smoking and chronic inflammatory stimulation are the major causes of COPD. Lung inflammation associated with COPD involves multiple cytokines, aggregation, and activation of neutrophils in the airway and lung tissue, and release of proteases and oxygen free radicals. In this study, a rat model of COPD was established by daily cigarette smoke exposure plus endotoxin treatment (the experimental group). Respiratory curves were recorded by the BL-420 biological signal collecting and processing system. Furthermore, the contents of inflammatory mediators, intercellular adhesion molecular (ICAM)-1 and interleukin (IL)-1β, in bronchoalveolar lavage fluid (BALF) were determined by enzyme linked immunosorbent assay for experimental, smoke-exposed only (control), and untreated (blank) rat groups. Protein expression levels of ICAM-1 and IL-1β in the lung tissue were also compared among groups by the immunohistochemical streptavidin-peroxidase method. The COPD model rats exhibited severe dyspnea and lung inflammation as evidenced by significantly prolonged expiratory duration, higher respiratory rate, elevated ICAM-1 and IL-1β in BALF, and higher ICAM-1 and IL-1β protein expression in lung tissue compared to control and blank group rats. Chronic cigarette smoke exposure plus endotoxin is a feasible and reliable model of COPD that recapitulates many clinical signs and pathogenic responses. ICAM-1 and IL-1β upregulation are possible early contributors to COPD-associated inflammatory lung injury.

Identification of key genes and biological pathways in chronic obstructive pulmonary disease using bioinformatics and next generation sequencing data analysis

“…Signaling pathways include immune system [109], signal transduction [110], extracellular matrix organization [111], adaptive immune system [112], neutrophil degranulation [113], innate immune system [114], metabolism [115], diseases of metabolism [116] and Hemostasis [117] were responsible for advancement of COPD. PTGS2 [118], IL6 [119], CSF3 [120], CXCL8 [121], CXCL1 [122], SOCS3 [123], CCL3 [124], CCL5 [125], VCAM1 [126], CXCL13 [127], CXCL5 [128], CXCL12 [129], FGG (fibrinogen gamma chain) [130], IL1B [131], AREG (amphiregulin) [132], SERPINE1 [133], OSM (oncostatin M) [134], CCL11 [135], MFAP4 [136], APLN (apelin) [137], IL1RN [138], IFNG (interferon gamma) [139], CX3CL1 [140], CDKN1A [141], ICAM1 [142], SNAI1 [143], CD34 [144], IL33 [145], FASLG (Fas ligand) [146], FGF7 [147], TNF (tumor necrosis factor) [148], GDF15 [149], CCL22 [150], IL2 [151], CXCR6 [152], KLF5 [153], MCL1 [154], SRF (serum response factor) [155], FABP4 [156], CYP2C19 [157], CXCR4 [158], FOXC1 [159], EPHX1 [160], ANXA1 [161], DUSP6 [162], CPA3 [163], MYH10 [164], ICOS (inducible T cell costimulator) [165], CD1C [166], CD96 [167], S100A9 [168], FKBP5 [169], HMOX1 [170], PRTN3 [171], MARCO (macrophage receptor with collagenous structure) [172], STAB1 [173], SIGLEC9 [174], SLC11A1 [175], BPI (bactericidal permeability increasing protein) [176], PGF (placental growth factor) [177], FASN (fatty acid synthase) [178], S100A4 […”

Dexmedetomidine‑mediated regulation of miR‑17‑3p in H9C2 cells after hypoxia/reoxygenation injury

“…Dysregulated synthesis of IL-6 has a pathological effect on inflammation ( 32 ). IL-1β, a member of the IL-1 family, has pro-inflammatory activity and promotes tissue injury ( 33 , 34 ). NF-κB was initially discovered in B cells, and is made up of a family of subunits consisting of p65/RelA, p50, p52, RelB and c-Rel ( 35 ).…”

Mechanism‐Based Disease Progression Model Describing Host‐Pathogen Interactions During the Pathogenesis of Acinetobacter baumannii Pneumonia

“…High IL‐1β expression levels have been linked to acute lung injury . Using albumin as an indicator of increased pulmonary permeability and injury, our model successfully captured lung injury dynamics with an indirect response model stimulated by IL‐1β.…”

“…41 High IL-1b expression levels have been linked to acute lung injury. [42][43][44] Using albumin as an indicator of increased pulmonary permeability and injury, our model successfully captured lung injury dynamics with an indirect response model stimulated by IL-1b. As the bacterial burden increased, the pro-inflammatory response was augmented, resulting in increased and prolonged lung injury.…”