Role of interleukin-6 in elastase-induced lung inflammatory changes in mice.
Interleukin-6 (IL-6) is known to be involved in the pathogenesis of various inflammatory diseases, but its role in the development of pulmonary emphysema remains unclear. Wild-type (WT) and IL-6-deficient mice received either phosphate-buffered saline (PBS) or porcine pancreatic elastase (PPE) intratracheally. The development of emphysema was determined by measuring the mean linear intercept (Lm). The lung specimens were also subjected to immunohistochemistry for single-stranded DNA to detect apoptotic cells. Lung mechanics and airway responsiveness to inhaled methacholine were analyzed. Bronchoalveolar lavage (BAL) fluid was subjected to evaluation of inflammatory cell accumulation and cytokine measurement. PPE treatment caused significant increases in Lm and lung compliance, which was attenuated by IL-6 deficiency. The increases in apoptotic cells in the lung were attenuated in IL-6 null mice. Airway responsiveness was not affected by PPE challenge or IL-6 deficiency. Intratracheal PPE increased the cell counts in BAL fluid throughout the observation, which was suppressed in IL-6 null mice. In BAL fluid, PPE-induced increases in the levels of macrophage inflammatory protein (MIP)-1alpha and eotaxin were mitigated by IL-6 deficiency. PPE-induced up-regulation of matrix metalloproteinase (MMP)-12 in the lung was attenuated by IL-6 deficiency. These results indicate that IL-6 may play an important role in the development of elastase-induced lung inflammatory changes.
Tasaka
Sadatomo
S
Division of Pulmonary Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. tasaka@cpnet.med.keio.ac.jp
Inoue
Ken-Ichiro
K
Miyamoto
Keisuke
K
Nakano
Yasushi
Y
Kamata
Hirofumi
H
Shinoda
Hiromi
H
Hasegawa
Naoki
N
Miyasho
Taku
T
Satoh
Masahiko
M
Takano
Hirohisa
H
Ishizaka
Akitoshi
A
D000403:Airway Resistance; D000818:Animals; D017209:Apoptosis; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000201:enzymology / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008170:Lung Compliance; D053508:Matrix Metalloproteinase 12 / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010196:Pancreatic Elastase; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D015656:Respiratory Mechanics; D013997:Time Factors
D016207:Cytokines; D015850:Interleukin-6; D010196:Pancreatic Elastase; D053508:Matrix Metalloproteinase 12