Cytokine and chemokine expression in cigarette smoke-induced lung injury in guinea pigs.
The guinea pig model of cigarette smoke (CS)-induced lung injury is known to exhibit many pathophysiological similarities to chronic obstructive pulmonary disease (COPD), but the expression profiles of inflammatory mediators in the lung are poorly understood. Quantitative real-time RT-PCR was used in this study to investigate the pulmonary expression profiles of cytokine and chemokine mRNA in response to single or repeated CS exposure in guinea pigs. A single CS exposure did not induce obvious inflammatory cell infiltration into the lungs, but it led to significant increases in the mRNA expression of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-8, and monocyte chemoattractant protein (MCP)-1, and decreases in IL-5 and granulocyte-macrophage colony-stimulating factor. Repeated CS exposure induced many features of COPD, such as marked accumulation of macrophages and neutrophils, augmented protease activities, lung structural alterations and increased airway resistance, accompanied by significant increases in the mRNA expression of IL-1beta and MCP-1 and decreases in IL-2, IL-5, transforming growth factor-beta, and eotaxin. In conclusion, in guinea pigs, inflammatory mediator changes in the lungs following cigarette smoke exposure are largely similar to those reported for smokers and/or chronic obstructive pulmonary disease patients. This model will therefore be useful to further understand the pathogenesis of chronic obstructive pulmonary disease.
Kubo
S
S
Inflammation Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd, 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan. satoshi.kubo@jp.astellas.com
Kobayashi
M
M
Masunaga
Y
Y
Ishii
H
H
Hirano
Y
Y
Takahashi
K
K
Shimizu
Y
Y
D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018925:Chemokines / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D011336:Probability; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012906:Smoke / Q000009:adverse effects*; D015996:Survival Rate; D014026:Nicotiana / Q000009:adverse effects*
D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D012906:Smoke