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Inflammatory compound lipopolysaccharide promotes the survival of GM‐CSF cultured dendritic cell via PI3 kinase‐dependent upregulation of Bcl‐x
Author(s) -
Chen Shun,
Li Xinchen,
Zhang Wenjie,
Zi Mengting,
Xu Yuekang
Publication year - 2018
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12051
Subject(s) - downregulation and upregulation , lipopolysaccharide , microbiology and biotechnology , innate immune system , immune system , biology , pi3k/akt/mtor pathway , mapk/erk pathway , dendritic cell , kinase , signal transduction , inflammation , immunology , biochemistry , gene
As professional antigen‐presenting cells, dendritic cells ( DC s) initiate and regulate immune responses against inflammation. The invasion of pathogens into the body, however, can in turn cause the change of DC s in both activity and viability, which ultimately affect immune homeostasis. The exact mechanisms that the bacteria utilize to alter the lifespan of DC s, however, are far from clear. In this study, we found that the bacterial wall compound lipopolysaccharide ( LPS ) can promote the survival of GM ‐ CSF ‐differentiated DC s ( GM ‐ DC s). At molecular levels, we demonstrated that GM ‐ DC s had distinct pattern of mRNA expression for anti‐apoptotic BCL ‐2 family members, of which, Bcl‐x increased significantly following LPS stimulation. Interestingly, specific inhibition of BCL ‐ XL protein alone was sufficient to remove the anti‐apoptotic effects of LPS on BM ‐ DC s. Further study of the signaling mechanisms revealed that although LPS can activate both Erk MAP kinase and PI 3 kinase pathways, only blocking of PI 3K abolished both Bcl‐x upregulation and the enhanced survival phenotype, suggesting that the PI 3K signaling mediated the upregulation of Bcl‐x for the LPS ‐induced pro‐survival in GM ‐ DC s. Collectively, this study unveils a molecular mechanism that DC s adapt to maintain innate immunity against the invasion of pathogens.