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Hypoxic modulation of hepatocyte responses to the cytokine interleukin‐22
Author(s) -
Budda Scott A,
Bhattarai Krishna,
Alexander Justine L,
Zenewicz Lauren A
Publication year - 2017
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 - 10.1038/icb.2016.107
Subject(s) - inflammation , cytokine , microbiology and biotechnology , stat protein , hypoxia (environmental) , stimulation , regulator , hepatocyte , hypoxia inducible factors , interleukin , biology , proinflammatory cytokine , signal transduction , chemistry , immunology , stat3 , endocrinology , oxygen , biochemistry , in vitro , organic chemistry , gene
The cytokine interleukin‐22 (IL‐22) is a potent regulator of tissue responses during inflammation. Depending on the context of inflammation, IL‐22 can have protective or inflammatory effects on epithelial cells. This dual nature of IL‐22 leads us to hypothesize that its activity must be exquisitely regulated to prevent host tissue damage. Environmental factors may act as a cellular cue as to how cells respond to IL‐22. Inflammatory environments are characterized by low oxygen and thus we examined whether cells respond differently to IL‐22 hypoxia compared with normoxia. In this study, we show that hepatocyte responses to IL‐22 stimulation are reduced in hypoxic environments. IL‐22 stimulation of hepatocytes incubated in low oxygen led to reduced levels of activated signal transducer and activator of transcription 3 and further downstream effects such as reduced induction of the anti‐microbial protein, lipocalin‐2. This modulation appears to be independent of the hypoxia‐inducible factor‐1α signaling pathway. Thus, hypoxia that accompanies chronic inflammation may be a mechanism to regulate the bioactivity of the dual‐natured IL‐22 cytokine.