Osteopontin Potentiates Pulmonary Inflammation and Fibrosis by Modulating IL-17/IFN-gamma-secreting T-cell Ratios in Bleomycin-treated Mice
Immune Network
;
: 142-149, 2015.
Article
in English
| WPRIM
| ID: wpr-148262
ABSTRACT
Lung fibrosis is a life-threatening disease caused by overt or insidious inflammatory responses. However, the mechanism of tissue injury-induced inflammation and subsequent fibrogenesis remains unclear. Recently, we and other groups reported that Th17 responses play a role in amplification of the inflammatory phase in a murine model induced by bleomycin (BLM). Osteopontin (OPN) is a cytokine and extracellular-matrix-associated signaling molecule. However, whether tissue injury causes inflammation and consequent fibrosis through OPN should be determined. In this study, we observed that BLM-induced lung inflammation and subsequent fibrosis was ameliorated in OPN-deficient mice. OPN was expressed ubiquitously in the lung parenchymal and bone-marrow-derived components and OPN from both components contributed to pathogenesis following BLM intratracheal instillation. Th17 differentiation of CD4+ alphabeta T cells and IL-17-producing gammadelta T cells was significantly reduced in OPN-deficient mice compared to WT mice. In addition, Th1 differentiation of CD4+ alphabeta T cells and the percentage of IFN-gamma-producing gammadelta T cells increased. T helper cell differentiation in vitro revealed that OPN was preferentially upregulated in CD4+ T cells under Th17 differentiation conditions. OPN expressed in both parenchymal and bone marrow cell components and contributed to BLM-induced lung inflammation and fibrosis by affecting the ratio of pathogenic IL-17/protective IFN-gamma T cells.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pneumonia
/
Pulmonary Fibrosis
/
Bleomycin
/
Fibrosis
/
Bone Marrow Cells
/
T-Lymphocytes
/
T-Lymphocytes, Helper-Inducer
/
Interleukin-17
/
Osteopontin
/
Inflammation
Limits:
Animals
Language:
English
Journal:
Immune Network
Year:
2015
Type:
Article
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