Role of galectin-3 in human pulmonary fibrosis.
BACKGROUND
Galectin-3 is a beta-galactoside-binding protein which is implicated in diverse physiological and pathological processes including human liver cirrhosis and a mouse lung fibrosis model. The aim of this study is to determine whether galectin-3 is involved in human lung fibrosis.


METHODS
We measured galectin-3 concentration in bronchoalveolar lavage fluid (BALF) and examined its expression in alveolar macrophages from patients with interstitial lung disorders using ELISA and immunohistochemical staining, respectively. Using monocyte/macrophage cell lines in vitro, we examined the effect of cytokines on galectin-3 expression, and the opposite similarly by RT-PCR and Western blotting. Finally, we performed Micro Boyden chamber assay and Sircoll assay to determine whether galectin-3 induces migration and collagen synthesis, respectively, in fibroblasts.


RESULTS
Galectin-3 was specifically increased in BALF from patients with idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia associated with collagen vascular disease (CVD-IP). Galectin-3 levels in BALF seemed to be lower in IPF and CVD-IP patients receiving corticosteroid therapy. Alveolar macrophages from IPF patients expressed more galectin-3 compared with those from control. Galectin-3 expression was induced by tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-gamma in a monocytic cell line U937. Galectin-3 also induced mRNA expression and protein production of TNF-alpha and interleukin (IL)-8 in a macrophage cell line THP-1. This lectin stimulated NIH-3T3 fibroblast to induce migration and collagen synthesis in vitro.


CONCLUSIONS
These results suggest that galectin-3 is involved in the pathogenesis of human IPF and CVD-IP by activating macrophages and fibroblasts.
Nishi
Yumiko
Y
Department of Internal Medicine, Toho University Sakura Medical Center, and Department of Allergy and Rheumatology, Chiba-East Hospital, National Hospital Organization, Japan.
Sano
Hideki
H
Kawashima
Tatsuo
T
Okada
Tomoaki
T
Kuroda
Toshihisa
T
Kikkawa
Kyoko
K
Kawashima
Sayaka
S
Tanabe
Masaaki
M
Goto
Tsukane
T
Matsuzawa
Yasuo
Y
Matsumura
Ryutaro
R
Tomioka
Hisao
H
Liu
Fu-Tong
FT
Shirai
Koji
K
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002465:Cell Movement / Q000502:physiology; D003094:Collagen / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D037502:Galectin 3 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017563:Lung Diseases, Interstitial / Q000188:drug therapy / Q000378:metabolism; D008262:Macrophage Activation / Q000502:physiology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014652:Vascular Diseases / Q000188:drug therapy / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D037502:Galectin 3; D003094:Collagen