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Hypoxia inhibits the maturation and function of murine bone marrow‐derived dendritic cells
Author(s) -
Zhang Lining,
Wang Qun,
Liu Chunmei,
Wang Xiaoyan,
Zhu Faliang,
Sun Wensheng
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.846.27
Subject(s) - chemokine , cd80 , bone marrow , c c chemokine receptor type 7 , cd86 , dendritic cell , microbiology and biotechnology , chemistry , hypoxia (environmental) , immune system , mmp9 , immunology , cancer research , biology , chemokine receptor , t cell , downregulation and upregulation , cd40 , cytotoxic t cell , in vitro , biochemistry , organic chemistry , oxygen , gene
Hypoxic is a prominent characteristic of inflammatory tissue lesions and solid tumor microenvironment. Under hypoxia condition, the changes of phenotype and function of infiltrated immune cells will affect the disease development and prognosis. It has been suggested that hypoxia might inhibit the production of matrix metalloproteinases (MMP) and the migration of human monocyte‐derived dendritic cells. However, the effects of hypoxia on murine bone marrow‐derived DC (BM‐DC) remain unclear. The present study is designed to compare the effects between hypoxic and normoxic conditions on the maturation and function of murine BM‐DC. We show here that hypoxia down‐regulated the expression of MHC II molecules and costimulatory molecules CD80, CD86 and CD137 on murine BM‐DC stimulated with LPS compared to that treated with normoxic condition, indicating that hypoxia inhibited the maturation of DC. Furthermore, hypoxia suppressed the expression of pro‐inflammatory cytokines (IL‐1, IL‐6, IL‐12 and TNF‐γ) and cell migration‐related gene (MMP9) in murine BM‐DC, but increased the levels of chemokine receptor (CCR7). Importantly, the hypoxia‐treated BM‐DC had reduced ability to stimulate the allogeneic CD4+T cell proliferation compared to normoxia‐differentiated BM‐DC. Thus, hypoxic microenvironment suppresses the maturation and function of murine BM‐DC demonstrated by downregulation of MHC Π and co‐stimulatory molecules and pro‐inflammatory cytokines, suggesting hypoxic DC as a possible target for tumor therapy. This work was supported by grants from the Natural Science Foundation of China (No. 30628015) and (No. 30671976) and National “973” program (No. 2006CB503803).